Latest revision as of 12:11, 23 July 2024

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Section editor
	Alaina J. Brown, MD, MPH Vanderbilt University Nashville, TN, USA LinkedIn

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
This page contains regimens which were not tested in biomarker-specific or histology-specific populations.
The following links will take you to biomarker-specific subpages:

Regimens for HRD-positive ovarian cancer are here.

The following links will take you to histology-specific subpages:

Regimens for low-grade serous ovarian cancer (LGSOC) are here.

51 regimens on this page 98 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

2022: Tew et al. Poly(ADP-Ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update PubMed
- 2020: Tew et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline link to PMC article PubMed
2021: Vanderpuye et al. Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline link to PMC article PubMed
2020: Konstantinopoulos et al. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline link to PMC article PubMed
2016: Wright et al. Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline PubMed

ESMO

2023: González-Martín et al. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2013: Ledermann et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Colombo et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Aebi & Castiglione. Newly and relapsed epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Aebi & Castiglione. Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Vasey. Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Vasey et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of epithelial ovarian carcinoma PubMed
2018: Ray-Coquard et al. Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Colombo et al. Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Colombo et al. Non-epithelial ovarian cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

ESMO/ESGO/ESP

2024: Ledermann et al. ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease PubMed
- 2019: Colombo et al. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease PubMed

NCCN

NCCN Guidelines - Ovarian Cancer, Including Fallopian Tube Cancer and Primary Peritoneal Cancer
- 2021: Armstrong et al. Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2016: Morgan et al. Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2013: Morgan et al. Ovarian cancer, version 2.2013. PubMed
- 2012: Morgan et al. Ovarian cancer, version 3.2012. PubMed
- 2011: Morgan et al. Epithelial ovarian cancer. PubMed
- 2008: Morgan et al. Ovarian cancer. Clinical practice guidelines in oncology. PubMed
- 2006: Morgan et al. Ovarian cancer. Clinical practice guidelines in oncology. PubMed
- 2004: Morgan et al. Ovarian cancer clinical practice guidelines. PubMed
NCCN Guidelines - Genetic/Familial High-Risk Assessment: Breast and Ovarian

SGO/ASCO

2016: Wright et al. Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline PubMed

Adjuvant therapy for early stage disease

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2003 (ICON1)	1991-2000	Phase 3 (E-esc)	Observation	Superior OS¹ (primary endpoint) OS60: 82% vs 74% (HR 0.67, 95% CI 0.50-0.90)

¹Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper).

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1

21-day cycle for 6 cycles

Regimen variant #2, 350 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Trimbos et al. 2003 (ACTION)	1990-2000	Phase 3 (E-esc)	Observation	Superior OS¹ (primary endpoint) OS60: 82% vs 74% (HR 0.67, 95% CI 0.50-0.90)

¹Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper). Cycle length was not specified in the paper; 21-day cycle is typical for this drug.

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) 350 mg/m² IV once on day 1

21-day cycle for 4 to 6 cycles (see note)

References

ACTION: Trimbos JB, Vergote I, Bolis G, Vermorken JB, Mangioni C, Madronal C, Franchi M, Tateo S, Zanetta G, Scarfone G, Giurgea L, Timmers P, Coens C, Pecorelli S; EORTC-ACTION collaborators. Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst. 2003 Jan 15;95(2):113-25. link to original article PubMed
1. Pooled update: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. link to original article PubMed
ICON1: Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, Torri V, Williams C, Lissoni A, Bonazzi C; ICON. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst. 2003 Jan 15;95(2):125-32. link to original article PubMed NCT00002477
1. Pooled update: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. link to original article PubMed

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen variant #1, 6/175

Study	Dates of enrollment	Evidence
Mannel et al. 2011 (GOG-0175)	1998-2006	Non-randomized part of phase 3 RCT

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for 3 cycles

Subsequent treatment

Observation versus Paclitaxel maintenance

Regimen variant #2, 7.5/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bell et al. 2006 (GOG 157)	1995-1998	Phase 3 (C)	CP x 6	Did not meet primary endpoint of RR

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 7.5 IV over 30 minutes once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for 3 cycles

References

GOG 157: Bell J, Brady MF, Young RC, Lage J, Walker JL, Look KY, Rose GS, Spirtos NM; Gynecologic Oncology Group. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Sep;102(3):432-9. Epub 2006 Jul 24. link to original article dosing details in abstract have been reviewed by our editors PubMed
GOG-0175: Mannel RS, Brady MF, Kohn EC, Hanjani P, Hiura M, Lee R, Degeest K, Cohn DE, Monk BJ, Michael H. A randomized phase III trial of IV carboplatin and paclitaxel x 3 courses followed by observation versus weekly maintenance low-dose paclitaxel in patients with early-stage ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jul;122(1):89-94. Epub 2011 May 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00003644

Neoadjuvant chemotherapy for advanced stage disease

Carboplatin & Paclitaxel (CP)

Regimen variant #1, AUC 5/175 x 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kehoe et al. 2015 (CHORUS)	2004-2010	Phase 3 (E-switch-ic)	Adjuvant CP	Non-inferior OS (primary endpoint) Median OS: 24.1 vs 22.6 mo (HR 0.87, 95% CI 0.72-1.05)

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

Interval debulking surgery, then adjuvant CP x 3

Regimen variant #2, AUC 5/175 x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Fagotti et al. 2016 (SCORPION)	2011-2014	Phase 3 (E-switch-ic)	Adjuvant CP	Did not meet primary endpoint of PFS	Superior QoL

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 6 cycles

Subsequent treatment

Interval debulking surgery

Regimen variant #3, AUC 6/175 x 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vergote et al. 2010 (EORTC 55971)	1998-2006	Phase 3 (E-switch-ic)	Adjuvant CP	Non-inferior OS (primary endpoint) Median OS: 30 vs 29 mo (HR 0.98, 90% CI 0.84-1.13)
Kehoe et al. 2015 (CHORUS)	2004-2010	Phase 3 (C)	Adjuvant CP	Non-inferior OS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

Interval debulking surgery, then adjuvant CP x 3

References

EORTC 55971: Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; EORTC-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT00003636
CHORUS: Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. Epub 2015 May 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN74802813
SCORPION: Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. Epub 2016 Mar 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01461850

First-line chemotherapy for advanced stage disease

Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Parmar et al. 1998 (ICON2)	1991-1996	Phase 3 (E-de-esc)	CAP	Did not meet primary endpoint of OS	Less toxic
Parmar et al. 2002 (ICON3)	1995-1998	Phase 3 (C)	1. CAP 2. Carboplatin & Paclitaxel	Did not meet primary endpoint of OS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1

21-day cycle for 6 cycles

Regimen variant #2, AUC 6, q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Parmar et al. 2002 (ICON3)	1995-1998	Phase 3 (C)	1. CAP 2. Carboplatin & Paclitaxel	Did not meet primary endpoint of OS
Banerjee et al. 2012 (SCOTROC 4)	2004-2009	Phase 3 (C)	Carboplatin; dose-escalated	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1

21-day cycle for 6 cycles

Regimen variant #3, AUC 6, q4wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gore et al. 1998	1987-1995	Phase 3 (C)	Carboplatin; AUC 12 x 4	Did not meet primary endpoint of OS24

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1

28-day cycle for 6 cycles

Regimen variant #4, AUC 9

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Markman et al. 2001 (GOG 114)	1992-1995	Phase 3 (E-esc)	See link	See link

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

Primary debulking surgery, with optimal debulking

Chemotherapy

Carboplatin (Paraplatin) AUC 9 IV once on day 1

28-day cycle for 2 cycles

Subsequent treatment

Adjuvant IP Cisplatin & IV Paclitaxel x 6

Regimen variant #5, 400 mg/m², q4wk

Historic variant

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Taylor et al. 1994	1981-10 to 1984-06	Phase 3 (C)	Cisplatin	Did not meet primary endpoint of ORR
Mangioni et al. 1989	1985-01 to 1987-02	Phase 3 (C)	Cisplatin	Did not meet endpoint

Chemotherapy

Carboplatin (Paraplatin) 400 mg/m² IV once on day 1

28-day cycle for 10 cycles

References

Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. link to original article dosing details in abstract have been reviewed by our editors PubMed
Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. link to original article dosing details in abstract have been reviewed by our editors PubMed
Gore M, Mainwaring P, A'Hern R, MacFarlane V, Slevin M, Harper P, Osborne R, Mansi J, Blake P, Wiltshaw E, Shepherd J; London Gynaecological Oncology Group. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. J Clin Oncol. 1998 Jul;16(7):2426-34. link to original article dosing details in abstract have been reviewed by our editors PubMed
ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ICON3: Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. link to original article PubMed
SCOTROC 4: Banerjee S, Rustin G, Paul J, Williams C, Pledge S, Gabra H, Skailes G, Lamont A, Hindley A, Goss G, Gilby E, Hogg M, Harper P, Kipps E, Lewsley LA, Hall M, Vasey P, Kaye SB; GCIG. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG. Ann Oncol. 2013 Mar;24(3):679-87. Epub 2012 Oct 5. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00098878

Carboplatin & Docetaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vasey et al. 2004 (SCOTROC-1)	1998-2000	Phase 3 (E-switch-ic)	Carboplatin & Paclitaxel	Did not meet primary endpoint of PFS

Preceding treatment

Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Dexamethasone (Decadron) 8 mg PO twice per day the day before, the day of, and day after docetaxel
ONE of the following 5-HT3 antagonists:
- Ondansetron (Zofran) 8 mg
- Granisetron 3 mg

21-day cycle for 6 cycles

References

SCOTROC-1: Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003998

Carboplatin & Pegylated liposomal doxorubicin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pignata et al. 2006 (MITO-2)	2003-2007	Phase 3 (E-switch-ic)	Carboplatin & Paclitaxel	Did not meet primary endpoint of PFS

Eligibility criteria for MITO-2 included: "a cytologic or histologic diagnosis of epithelial ovarian cancer (stage IC to IV according to International Federation of Gynecology and Obstetrics staging system).

Preceding treatment

Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given first
Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV over 60 minutes once on day 1, given second

Supportive therapy

"No prophylactic use of G-CSF was recommended. Therapeutic and prophylactic use of G-CSF was allowed for febrile or afebrile grade 4 neutropenia."

21-day cycle for 3 to 6 cycles All patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.

References

MITO-2: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00326456
1. Update: Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. Epub 2011 Aug 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Carboplatin & Gemcitabine (GCb)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gordon et al. 2011 (B9E-US-S302)	2002-2006	Phase 3 (E-switch-ic)	Carboplatin & Paclitaxel	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8, given first

21-day cycle for up to 6 cycles

Subsequent treatment

B9E-US-S302, patients with CR: optional paclitaxel consolidation

References

B9E-US-S302: Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00191646

Carboplatin & Paclitaxel (CP)

TC: Taxol (Paclitaxel) & Carboplatin
PC: Paclitaxel & Carboplatin

Regimen variant #1, q1wk AUC 2/60

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pignata et al. 2014 (MITO-7)	2008-2012	Phase 3 (E-switch-ic)	TC; q3wk AUC 6/175	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 2 IV once on day 1
Paclitaxel (Taxol) 60 mg/m² IV once on day 1

7-day cycle for 18 cycles

Regimen variant #2, q3wk AUC 5, q1wk 80

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2021 (JAVELIN Ovarian 100)	2016-2018	Phase 3 (C)	1. CP & Avelumab 2. CP, then Avelumab	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

21-day cycle for 6 cycles

Regimen variant #3, q3wk AUC 5/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Neijt et al. 2000	1994-1997	Phase 3 (E-switch-ic)	Cisplatin & Paclitaxel	Did not meet primary endpoint of PFS
du Bois et al. 2006 (AGO-OVAR 5)	1997-2000	Phase 3 (C)	TEC	Did not meet primary endpoint of OS
Vasey et al. 2004 (SCOTROC-1)	1998-2000	Phase 3 (C)	Carboplatin & Docetaxel	Did not meet primary endpoint of PFS
Möbus et al. 2007 (HIDOC-EIS)	1998-2004	Phase 3 (C)	High-dose chemotherapy with auto HSCT	Did not meet primary endpoint of PFS
Lindemann et al. 2012 (EORTC 55981)	1999-2001	Phase 3 (C)	TEC	Did not meet primary endpoint of PFS
Hoskins et al. 2010 (EORTC 55012)	2001-2005	Phase 3 (C)	Cisplatin & Topotecan, then TC	Did not meet primary endpoint of PFS	Less toxic
du Bois et al. 2010 (AGO-OVAR 9)	2002-2004	Phase 3 (C)	TCG	Did not meet primary endpoint of OS
Pignata et al. 2006 (MITO-2)	2003-2007	Phase 3 (C)	Carboplatin & PLD	Did not meet primary endpoint of PFS
du Bois et al. 2015 (AGO-OVAR 12)	2009-2011	Phase 3 (C)	TC & Nintedanib	Seems to have inferior PFS
Fagotti et al. 2016 (SCORPION)	2011-2014	Phase 3 (C)	TC; neoadjuvant	Did not meet primary endpoint of PFS	Inferior QoL
Clamp et al. 2019 (ICON8)	2011-2014	Phase 3 (C)	1. TC; q1wk AUC 2/80 2. TC; q3wk AUC 6, q1wk 80 ("dose-dense")	Did not meet co-primary endpoints of PFS/OS
Vergote et al. 2019 (TRINOVA-3)	2012-2014	Phase 3 (C)	TC & Trebananib	Did not meet primary endpoint of PFS
Monk et al. 2021 (JAVELIN Ovarian 100)	2016-2018	Phase 3 (C)	1. CP & Avelumab 2. CP, then Avelumab	Did not meet primary endpoint of PFS

Note: In MITO-2, all patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.

Preceding treatment

Neijt et al. 2000: Primary debulking surgery was recommended
SCOTROC-1, MITO-2, AGO-OVAR 12, SCORPION: Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

Supportive therapy

(per Vasey et al. 2004):
Dexamethasone (Decadron) 20 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel
One of the following antihistamines:
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Chlorpheniramine (Chlor-Trimeton) 10 mg IV once on day 1; 30 minutes prior to paclitaxel
One of the following H2-blockers
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 8 mg
- Granisetron 3 mg

21-day cycle for 6 or more cycles (see note)

Regimen variant #4, q3wk AUC 6, q1wk 80

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016)	2003-2005	Phase 3 (E-switch-ic)	TC; q3wk AUC 6/180	Seems to have superior OS (secondary endpoint) OS36: 72.1% vs 65.1% (HR 0.75, 95% CI 0.57-0.98) Superior PFS (primary endpoint) Median PFS: 28 vs 17.2 mo (HR 0.71, 95% CI 0.58-0.88)
Coleman et al. 2019 (VELIA)	2015-2017	Phase 3 (C)	1. CP & Veliparib x 6	Not reported
Coleman et al. 2019 (VELIA)	2015-2017	Phase 3 (C)	2. CP & Veliparib x 6, then Veliparib maint.	Inferior PFS
Monk et al. 2021 (JAVELIN Ovarian 100)	2016-2018	Phase 3 (C)	1. CP & Avelumab 2. CP, then Avelumab	Did not meet primary endpoint of PFS
Nagao et al. 2023 (iPocc)	2010-05 to 2016-08	Phase 2/3 (C)	IP Carboplatin & Paclitaxel	Seems to have inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1
Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

Supportive therapy

"Standard premedication"

21-day cycle for 6 to 9 cycles, depending on response and protocol

Regimen variant #5, q3wk AUC 6/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lhommé et al. 2008	1997-1999	Phase 3 (C)	Paclitaxel & Valspodar	Did not meet primary endpoint of TTP
Vergote et al. 2010 (EORTC 55971)	1998-2006	Phase 3 (C)	TC x 3, then interval debulking, then TC x 3	Non-inferior OS
Gordon et al. 2011 (B9E-US-S302)	2002-2006	Phase 3 (C)	Carboplatin & Gemcitabine	Did not meet primary endpoint of PFS
Bookman et al. 2009 (ICON5)	2001-2004	Phase 3 (C)	1. TCG 2. TC & PLD 3. TC & Topotecan	Did not meet primary endpoint of OS
Alberts et al. 2008 (GRACES)	2002-2004	Phase 3 (C)	CP & IFN gamma-1b	Did not meet primary endpoint of OS
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (C)	1. TC & Bevacizumab x 6	Might have inferior PFS
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (C)	2. TC & Bevacizumab x 22	Inferior PFS
Perren et al. 2011 (ICON7)	2006-2009	Phase 3 (C)	Carboplatin, Paclitaxel, Bevacizumab	Did not meet co-primary endpoints of PFS/OS¹
Sugiyama et al. 2016 (JGOG3017/GCIG)	2006-2011	Phase 3 (C)	Cisplatin & Irinotecan	Did not meet primary endpoint of PFS
Pignata et al. 2014 (MITO-7)	2008-2012	Phase 3 (C)	TC; q1wk AUC 2/60	Did not meet primary endpoint of PFS
du Bois et al. 2015 (AGO-OVAR 12)	2009-2011	Phase 3 (C)	TC & Nintedanib	Seems to have inferior PFS
Chan et al. 2016 (GOG-0262)	2010-2012	Phase 3 (C)	TC; dose-dense	Did not meet primary endpoint of PFS
Clamp et al. 2019 (ICON8)	2011-2014	Phase 3 (C)	1. TC; q1wk AUC 2/80 2. TC; q3wk AUC 6, q1wk 80 ("dose-dense")	Did not meet co-primary endpoints of PFS/OS
Vergote et al. 2019 (TRINOVA-3)	2012-2014	Phase 3 (C)	TC & Trebananib	Did not meet primary endpoint of PFS
Coleman et al. 2019 (VELIA)	2015-2017	Phase 3 (C)	1. TC & Veliparib x 6	Not reported
Coleman et al. 2019 (VELIA)	2015-2017	Phase 3 (C)	2. TC & Veliparib x 6, then Veliparib maint.	Inferior PFS
Monk et al. 2021 (JAVELIN Ovarian 100)	2016-2018	Phase 3 (C)	1. CP & Avelumab 2. CP, then Avelumab	Did not meet primary endpoint of PFS

¹Reported efficacy for ICON7 is based on the 2015 update.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for up to 6 to 8 cycles

Subsequent treatment

B9E-US-S302, patients with CR: Optional paclitaxel consolidation

Regimen variant #6, q3wk AUC 6/180

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016)	2003-2005	Phase 3 (C)	TC; dose-dense	Seems to have inferior OS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1
Paclitaxel (Taxol) 180 mg/m² IV over 3 hours once on day 1

Supportive therapy

"Standard premedication"

21-day cycle for 6 to 9 cycles, depending on response

Regimen variant #7, AUC 6/185

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
du Bois et al. 2003 (AGO-OVAR 3)	1995-1997	Phase 3 (E-switch-ic)	Cisplatin & Paclitaxel	Non-inferior PFS	Superior QoL

Preceding treatment

Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 to 60 minutes once on day 1, given second
Paclitaxel (Taxol) 185 mg/m² (maximum dose of 400 mg) IV over 3 hours once on day 1, given first

21-day cycle for 6 or more cycles

Regimen variant #8, q3wk AUC 7/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Aravantinos et al. 2005	1995-1999	Phase 3 (C)	CP/Cisplatin & Paclitaxel	Did not meet primary endpoint of OS
Aravantinos et al. 2008	1999-2004	Phase 3 (C)	Cisplatin, Doxorubicin, Paclitaxel	Might have inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 7 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for 6 cycles

Regimen variant #9, q3wk AUC 7.5/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ozols et al. 2003 (GOG 158)	Not reported	Phase 3 (E-switch-ic)	Cisplatin & Paclitaxel	Seems to have non-inferior RFS (primary endpoint)

Chemotherapy

Carboplatin (Paraplatin) AUC 7.5 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive therapy

Dexamethasone (Decadron) with one of the following options:
- 20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
- 20 mg IV once on day 1; 30 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycle for 6 cycles

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TRINOVA-3: Vergote I, Scambia G, O'Malley DM, Van Calster B, Park SY, Del Campo JM, Meier W, Bamias A, Colombo N, Wenham RM, Covens A, Marth C, Raza Mirza M, Kroep JR, Ma H, Pickett CA, Monk BJ; TRINOVA-3/ENGOT-ov2/GOG-3001 investigators. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):862-876. Epub 2019 May 7. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01493505
VELIA: Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. Epub 2019 Sep 28. link to original article link to PMC article PubMed NCT02470585
ICON8: Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Hook J, Coyle C, Blagden S, Brenton JD, Naik R, Perren T, Sundar S, Cook AD, Gopalakrishnan GS, Gabra H, Lord R, Dark G, Earl HM, Hall M, Banerjee S, Glasspool RM, Jones R, Williams S, Swart AM, Stenning S, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. Lancet. 2019 Dec 7;394(10214):2084-2095. Epub 2019 Nov 29. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01654146
1. Update: Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Gallardo-Rincon D, Blagden S, Brenton J, Perren TJ, Sundar S, Lord R, Dark G, Hall M, Banerjee S, Glasspool RM, Hanna CL, Williams S, Scatchard KM, Nam H, Essapen S, Parkinson C, McAvan L, Swart AM, Popoola B, Schiavone F, Badrock J, Fananapazir F, Cook AD, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):919-930. Epub 2022 Jun 8. link to original article link to PMC article PubMed
JAVELIN Ovarian 100: Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC, Bhoola SM, Sohn J, Yonemori K, Stewart RA, Zhang X, Perkins Smith J, Linn C, Ledermann JA. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Sep;22(9):1275-1289. Epub 2021 Aug 4. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02718417
iPocc: Nagao S, Fujiwara K, Yamamoto K, Tanabe H, Okamoto A, Takehara K, Saito M, Fujiwara H, Tan DSP, Yamaguchi S, Adachi S, Kikuchi A, Hirasawa T, Yokoi T, Nagai T, Sato T, Kamiura S, Fujishita A, Loong W-W, Chan K, Syks P, Olawaye A, Ryu S-Y, Shigeta H, Kondo E, Yokoyama Y, Matsumoto T, Hasegawa K, Enomoto T. Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial. NEJM Evid. 2023;2(5). link to original article dosing details in supplement have been reviewed by our editors PubMed jRCTs031180141
FLORA-5: NCT04498117
KEYLYNK-001: NCT03740165

Carboplatin & Paclitaxel (CP) & Bevacizumab

TC-BEV: Taxol (Paclitaxel), Carboplatin, BEVacizumab

Regimen variant #1, q3wk paclitaxel, standard-dose bevacizumab x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (E-RT-esc)	1. Carboplatin & Paclitaxel	Might have superior PFS (primary endpoint) Median PFS: 11.2 vs 10.3 mo (HR 0.91, 95% CI 0.80-1.04) Did not meet secondary endpoint of OS¹ Median OS: 40.8 vs 41.1 mo (HR 1.06, 95% CI 0.94-1.20)
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (E-RT-esc)	2. CP & Bevacizumab x 22	Not reported
Chan et al. 2016 (GOG-0262)	2010-2012	Phase 3 (C)	TC-Bev; dose-dense	Did not meet primary endpoint of PFS
Moore et al. 2021 (IMagyn050)	2017-2019	Phase 3 (C)	CP, Atezolizumab, Bevacizumab	Did not meet primary endpoint of PFS

¹Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.
Note: Decision to use bevacizumab in GOG-0262 was at the discretion of the patient; it was not a randomization.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Targeted therapy

Bevacizumab (Avastin) as follows:
- Cycles 2 to 6: 15 mg/kg IV once on day 1

21-day cycle for 6 cycles

Subsequent treatment

GOG-0262 & IMagyn050: Bevacizumab maintenance

Regimen variant #2, q3wk paclitaxel, standard-dose bevacizumab x 22

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (E-RT-esc)	1. Carboplatin & Paclitaxel	Superior PFS (primary endpoint) Median PFS: 14.1 vs 10.3 mo (HR 0.72, 95% CI 0.625-0.82) Did not meet secondary endpoint of OS¹ Median OS: 43.4 vs 41.1 mo (HR 0.96, 95% CI 0.85-1.09)
Burger et al. 2011 (GOG-0218)	2005-2009	Phase 3 (E-RT-esc)	2. CP & Bevacizumab x 6	Not reported

¹Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 IV over 30 minutes once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV over 3 hours once on day 1

Targeted therapy

Bevacizumab (Avastin) as follows:
- Cycles 2 to 22: 15 mg/kg IV once on day 1

21-day cycle for 22 cycles

Regimen variant #3, q3wk paclitaxel, low-dose bevacizumab

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Perren et al. 2011 (ICON7)	2006-2009	Phase 3 (E-esc)	Carboplatin & Paclitaxel	Did not meet co-primary endpoints of PFS/OS¹

¹Reported efficacy is based on the 2015 update.
Note: Bevacizumab was not given with cycle 1 if chemotherapy starts within 4 weeks of surgery. The protocol linked from Perren et al. 2011 clarifies that the recommended carboplatin dose was AUC 6, but that it could be adjusted per standard practice

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 to 6 IV over 30 to 60 minutes once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV over 3 hours once on day 1

Targeted therapy

Bevacizumab (Avastin) as follows:
- Cycles 1 to 6: 7.5 mg/kg IV once on day 1
- Cycles 7 to 18: 15 mg/kg IV once on day 1

21-day cycle for 18 cycles

Regimen variant #4, weekly paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Walker et al. 2019 (GOG-252)	2009-2011	Phase 3 (C)	1. IP Carboplatin, IV Paclitaxel & Bevacizumab 2. IP Cisplatin & Paclitaxel, IV Paclitaxel & Bevacizumab	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

Targeted therapy

Bevacizumab (Avastin) as follows:
- Cycles 2 to 6: 15 mg/kg IV once on day 1

21-day cycle for 6 cycles

Subsequent treatment

Bevacizumab maintenance

References

GOG-0218: Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00262847
1. PRO analysis: Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. Epub 2012 Dec 4. link to original article link to PMC article PubMed
2. Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
ICON7: Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00483782
1. HRQoL analysis: Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013 Mar;14(3):236-43. Epub 2013 Jan 18. link to original article link to PMC article PubMed
2. Update: Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ; ICON. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):928-36. Epub 2015 Jun 23. link to original article link to PMC article PubMed
GOG-0262: Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O'Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016 Feb 25;374(8):738-48. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01167712
GOG-252: Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00951496
IMagyn050: Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J, Willmott L, Colombo N, Thomes-Pepin J, Liontos M, Gold MA, Garcia Y, Sharma SK, Darus CJ, Aghajanian C, Okamoto A, Wu X, Safin R, Wu F, Molinero L, Maiya V, Khor VK, Lin YG, Pignata S. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021 Jun 10;39(17):1842-1855. Epub 2021 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03038100
1. Update: Pignata S, Bookman M, Sehouli J, Miller A, Penson RT, Taskiran C, Anderson C, Hietanen S, Myers T, Madry R, Willmott L, Lortholary A, Thomes-Pepin J, Aghajanian C, McCourt C, Stuckey A, Wu X, Nishio S, Copeland LJ, He Y, Molinero L, Patel S, Lin YG, Khor VK, Moore KN. Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer. Gynecol Oncol. 2023 Oct;177:20-31. Epub 2023 Aug 23. link to original article link to PMC article PubMed
DUO-O: NCT03737643
FIRST_OV: NCT03602859

Carboplatin & Paclitaxel (CP) & Nintedanib

CP & Nintedanib: Carboplatin, Paclitaxel, Nintedanib
TC & Nintedanib: Taxol (Paclitaxel), Carboplatin, Nintedanib

Regimen variant #1, q3wk AUC 5/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
du Bois et al. 2015 (AGO-OVAR 12)	2009-2011	Phase 3 (E-esc)	TC	Seems to have superior PFS (primary endpoint) Median PFS: 17.2 vs 16.6 mo (HR 0.84, 95% CI 0.72-0.98)

Preceding treatment

Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

Targeted therapy

Nintedanib (Vargatef) 200 mg PO twice per day on days 2 to 21

21-day cycles

Regimen variant #2, q3wk AUC 6/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
du Bois et al. 2015 (AGO-OVAR 12)	2009-2011	Phase 3 (E-esc)	TC	Seems to have superior PFS (primary endpoint) Median PFS: 17.2 vs 16.6 mo (HR 0.84, 95% CI 0.72-0.98)

Preceding treatment

Primary debulking surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

Targeted therapy

Nintedanib (Vargatef) 200 mg PO twice per day on days 2 to 21

21-day cycles

References

AGO-OVAR 12: du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, Denison U, Vergote I, Del Campo JM, Ottevanger P, Heubner M, Minarik T, Sevin E, de Gregorio N, Bidziński M, Pfisterer J, Malander S, Hilpert F, Mirza MR, Scambia G, Meier W, Nicoletto MO, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2016 Jan;17(1):78-89. Epub 2015 Nov 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01015118
1. Update: Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. link to original article PubMed

Cisplatin & Paclitaxel

TP: Taxol (Paclitaxel) & Platinol (Cisplatin)
PT: Platinol (Cisplatin) & Taxol (Paclitaxel)

Regimen variant #1, 75/135

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
McGuire et al. 1996 (GOG 111)	Not reported	Phase 3 (E-RT-switch-ic)	Cisplatin & Cyclophosphamide	Superior OS Median OS: 38 vs 24 mo (RR 0.60, 95% CI 0.50-0.80)
Muggia et al. 2000 (GOG 132)	1992-1994	Phase 3 (C)	1. Cisplatin 2. Paclitaxel	Did not meet primary endpoint of PFS
Markman et al. 2001 (GOG 114)	1992-1995	Phase 3 (C)	Carboplatin, then IP Cisplatin & IV Paclitaxel	Seems to have inferior OS
Ozols et al. 2003 (GOG 158)	Not reported	Phase 3 (C)	Carboplatin & Paclitaxel	Seems to have non-inferior RFS
Rose et al. 2004 (GOG 152)	1994-2001	Phase 3 (C)	Cisplatin & Paclitaxel; with interval debulking	Did not meet primary endpoint of OS
Armstrong et al. 2006 (GOG 172)	1998-2001	Phase 3 (C)	IP Cisplatin & Paclitaxel	Seems to have inferior OS
Spriggs et al. 2007 (GOG 162)	Not reported	Phase 3 (C)	Cisplatin & Paclitaxel; prolonged-infusion paclitaxel	Did not meet primary endpoint of OS

Note: Some references specify to give the cisplatin after the paclitaxel (i.e., on day 2)

Preceding treatment

GOG 111, 132, 152: Primary debulking surgery, with suboptimal debulking
GOG 114, 158, 172: Primary debulking surgery, with optimal debulking

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1 or 2
Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive therapy

(details vary depending on reference):
Dexamethasone (Decadron) with one of the following options:
- 20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
- 20 mg IV once on day 1; 30 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
"Hydration and antiemetic agents" once on day 1, prior to cisplatin

21-day cycle for 6 cycles

Regimen variant #2, 75/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Piccart et al. 2000 (OV10)	1994-04 to 1995-08	Phase 3 (E-RT-switch-ic)	Cisplatin & Cyclophosphamide	Superior OS
Neijt et al. 2000	1994-1997	Phase 3 (C)	Carboplatin & Paclitaxel	Did not meet primary endpoint of PFS
Mouratidou et al. 2007	1998-2002	Phase 3 (E-switch-ic)	Cisplatin & Cyclophosphamide	Did not meet primary endpoint of PFS
van der Burg et al. 2014	1999-2006	Phase 3 (C)	Cisplatin & Paclitaxel; weekly paclitaxel	Did not meet primary endpoint of PFS

Preceding treatment

OV10: Primary debulking surgery, with optimal or suboptimal debulking
Neijt et al. 2000: Primary debulking surgery was recommended

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 6 or more cycles

Regimen variant #3, 75/185

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
du Bois et al. 2003 (AGO-OVAR 3)	1995-1997	Phase 3 (C)	Carboplatin & Paclitaxel	Non-inferior PFS	Inferior QoL

Preceding treatment

Primary debulking surgery

Chemotherapy

Cisplatin (Platinol) 75 mg/m² (maximum dose of 165 mg) IV over 30 minutes once on day 1, given second
Paclitaxel (Taxol) 185 mg/m² (maximum dose of 400 mg) IV over 3 hours once on day 1, given first

21-day cycle for 6 or more cycles

References

GOG 111: McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 132: Muggia FM, Braly PS, Brady MF, Sutton G, Niemann TH, Lentz SL, Alvarez RD, Kucera PR, Small JM. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2000 Jan;18(1):106-15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
OV10: Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 158: Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. Epub 2003 Jul 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed
AGO-OVAR 3: du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, Pfisterer J; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 152: Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM; Gynecologic Oncology Group. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004 Dec 9;351(24):2489-97. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002568
GOG 172: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003322
1. Subgroup analysis: Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. link to original article dosing details in abstract have been reviewed by our editors PubMed
GOG 162: Spriggs DR, Brady MF, Vaccarello L, Clarke-Pearson DL, Burger RA, Mannel R, Boggess JF, Lee RB, Hanly M. Phase III randomized trial of intravenous cisplatin plus a 24- or 96-hour infusion of paclitaxel in epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Oct 1;25(28):4466-71. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00002717
van der Burg ME, Onstenk W, Boere IA, Look M, Ottevanger PB, de Gooyer D, Kerkhofs LG, Valster FA, Ruit JB, van Reisen AG, Goey SH, van der Torren AM, ten Bokkel Huinink D, Kok TC, Verweij J, van Doorn HC. Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer. Eur J Cancer. 2014 Oct;50(15):2592-601. Epub 2014 Aug 2. link to original article dosing details in abstract have been reviewed by our editors PubMed

Intraperitoneal therapy

IP Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Nagao et al. 2023 (iPocc)	2010-05 to 2016-08	Phase 2/3 (E-switch-ic)	IV Carboplatin & Paclitaxel	Seems to have superior PFS (primary endpoint) Median PFS: 23.5 vs 20.7 mo (HR 0.83, 95% CI 0.69-0.99)

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IP once on day 1
Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

21-day cycle for 6 cycles

References

iPocc: Nagao S, Fujiwara K, Yamamoto K, Tanabe H, Okamoto A, Takehara K, Saito M, Fujiwara H, Tan DSP, Yamaguchi S, Adachi S, Kikuchi A, Hirasawa T, Yokoi T, Nagai T, Sato T, Kamiura S, Fujishita A, Loong W-W, Chan K, Syks P, Olawaye A, Ryu S-Y, Shigeta H, Kondo E, Yokoyama Y, Matsumoto T, Hasegawa K, Enomoto T. Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial. NEJM Evid. 2023;2(5). link to original article dosing details in supplement have been reviewed by our editors PubMed jRCTs031180141

IP Cisplatin & Paclitaxel

Regimen variant #1, IV paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Markman et al. 2001 (GOG 114)	1992-1995	Phase 3 (E-switch-ic)	See link	See link

Preceding treatment

First-line carboplatin; AUC 9 x 2

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IP once on day 2
Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours, started on day 1

21-day cycle for 6 cycles

Regimen variant #2, IV/IP paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Armstrong et al. 2006 (GOG 172)	1998-2001	Phase 3 (E-switch-ic)	Cisplatin & Paclitaxel; IV	Seems to have superior OS (co-primary endpoint) Median OS: 65.6 vs 49.7 mo (RR 0.75, 95% CI 0.58-0.97)

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IP rapid infusion once on day 2
- Walker et al. 2006 instructs that the patient be rolled onto 4 different positions every 15 minutes to evenly distribute cisplatin
Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours, started on day 1, then 60 mg/m² IP rapid infusion once on day 8

Supportive therapy

(Varies per reference)
"Standard premedication" for paclitaxel
"Hydration and antiemetic agents" prior to cisplatin
Intraperitoneal doses of cisplatin and paclitaxel are reconstituted in 2 liters of warm normal saline before infusion
Additional 1 liter normal saline to be infused immediately after intraperitoneal paclitaxel
Supportive medications left to investigator discretion

21-day cycle for 6 cycles

References

GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GOG 172: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003322
1. Subgroup analysis: Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Maintenance after first-line therapy

Altretamine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Rothenberg et al. 2001 (SWOG-9326)	1993-1997	Phase 2

Chemotherapy

Altretamine (Hexalen) 260 mg/m²/day PO on days 1 to 14, split into 4 daily doses

28-day cycle for 6 cycles

References

SWOG-9326: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. link to original article dosing details in abstract have been reviewed by our editors PubMed
1. Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article PubMed

Bevacizumab monotherapy

Regimen variant #1, 16 cycles

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Walker et al. 2019 (GOG-252)	2009-2011	Non-randomized part of phase 3 RCT
Pfisterer et al. 2023 (BOOST)	2011-11-11 to 2013-08-06	Phase 3 (C)	Bevacizumab x 30 mo	Did not meet primary endpoint of PFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

BOOST: First-line Carboplatin, Paclitaxel, Bevacizumab x 6
GOG-252: First-line Carboplatin, Paclitaxel, Bevacizumab x 6 versus IP Carboplatin, IV Paclitaxel & Bevacizumab x 6 versus IP Cisplatin & Paclitaxel, IV Paclitaxel & Bevacizumab x 6

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycle for up to 16 cycles

Regimen variant #2, indefinite

Study	Dates of enrollment	Evidence
Chan et al. 2016 (GOG-0262)	2010-2012	Non-randomized part of phase 3 RCT

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

First-line Carboplatin, Paclitaxel, Bevacizumab x 6

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles

References

GOG-0262: Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O'Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016 Feb 25;374(8):738-48. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01167712
GOG-252: Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00951496
BOOST: Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Lueck HJ, Emons G, Meier W, Gropp-Meier M, Schroeder W, de Gregorio N, Hilpert F, Harter P. Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial. J Clin Oncol. 2023 Feb 1;41(4):893-902. Epub 2022 Nov 4. link to original article PubMed NCT01462890

Niraparib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
González-Martín et al. 2019 (PRIMA_OV)	2016-2018	Phase 3 (E-RT-esc)	Placebo	Superior PFS¹ (primary endpoint) Median PFS: 13.8 vs 8.2 mo (HR 0.66, 95% CI 0.56-0.79)
Li et al. 2023 (PRIME_OV)	2018-06-29 to 2019-11-11	Phase 3 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 24.8 vs 8.3 mo (HR 0.45, 95% CI 0.34-0.60)

¹Reported efficacy for PRIMA_OV is for the overall population and is based on the 2023 update.
Note: there are studies named PRIMA and PRIME in other cancer types, not to be confused with these.

Preceding treatment

First-line platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.

Targeted therapy

Niraparib (Zejula) by the following laboratory- and weight-based criteria:
- Less than 77 kg OR platelet count less than 150 x 10⁹/L: 200 mg PO once per day on days 1 to 28
- 77 kg or more AND platelet count 150 x 10⁹/L or more: 300 mg PO once per day on days 1 to 28

28-day cycle for up to 39 cycles (3 years)

References

PRIMA_OV: González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. Epub 2019 Sep 28. link to original article PubMed NCT02655016
1. Update: González-Martín A, Pothuri B, Vergote I, Graybill W, Lorusso D, McCormick CC, Freyer G, Backes F, Heitz F, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Malinowska IA, Shtessel L, Compton N, Mirza MR, Monk BJ. Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023 Aug;189:112908. Epub 2023 May 3. link to original article PubMed
2. HRQoL analysis: Pothuri B, Han S, Chase DM, Heitz F, Burger RA, Gaba L, Van Le L, Guerra E, Bender D, Korach J, Cloven N, Churruca C, Follana P, DiSilvestro P, Baurain JF, Jardon K, Pisano C, Peen U, Mäenpää J, Gupta D, Bacqué E, Li Y, Compton N, Antonova J, Monk BJ, González-Martín A. Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial. Gynecol Oncol. 2024 May;184:168-177. Epub 2024 Feb 6. link to original article PubMed
PRIME_OV: Li N, Zhu J, Yin R, Wang J, Pan L, Kong B, Zheng H, Liu J, Wu X, Wang L, Huang Y, Wang K, Zou D, Zhao H, Wang C, Lu W, Lin A, Lou G, Li G, Qu P, Yang H, Zhang Y, Cai H, Pan Y, Hao M, Liu Z, Cui H, Yang Y, Yao S, Zhen X, Hang W, Hou J, Wang J, Wu L. Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1230-1237. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT03709316
AGO-OVAR 28: NCT05009082

Paclitaxel monotherapy

Regimen variant #1, 135 mg/m² q4wk

Study	Dates of enrollment	Evidence
Gordon et al. 2011 (B9E-US-S302)	2002-2006	Non-randomized part of phase 3 RCT

Preceding treatment

First-line Carboplatin & Gemcitabine x 6 versus Carboplatin & Paclitaxel x 6

Chemotherapy

Paclitaxel (Taxol) 135 mg/m² IV once on day 1

28-day cycle for up to 12 cycles

Regimen variant #2, 175 mg/m² q3wk x 3

Study	Dates of enrollment	Evidence
Micha et al. 2005	2002-07 to 2003-08	Phase 2, fewer than 20 patients in this subgroup

Preceding treatment

First-line Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 60 minutes once on day 1

21-day cycle for 3 cycles

Regimen variant #3, 175 mg/m² q3wk x 12

Study	Dates of enrollment	Evidence
Micha et al. 2005	2002-07 to 2003-08	Phase 2, fewer than 20 patients in this subgroup

Preceding treatment

First-line Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 60 minutes once on day 1

21-day cycle for 12 cycles

Regimen variant #4, 175 mg/m² q4wk x 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Markman et al. 2003 (GOG 178)	1997-2001	Phase 3 (C)	Paclitaxel x 12	Inferior PFS

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

28-day cycle for 3 cycles

Regimen variant #5, 175 mg/m² q4wk x 12

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Markman et al. 2003 (GOG 178)	1997-2001	Phase 3 (E-esc)	Paclitaxel x 3	Superior PFS (primary endpoint) Median PFS: 28 vs 21 mo (HR 0.43, 99% CI 0.20-0.93) 2.31 (99% confidence interval, 1.08 to 4.94

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

28-day cycle for 12 cycles

References

GOG 178: Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; SWOG; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003120
1. Update: Markman M, Liu PY, Moon J, Monk BJ, Copeland L, Wilczynski S, Alberts D. Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m²) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial. Gynecol Oncol. 2009 Aug;114(2):195-8. Epub 2009 May 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Micha JP, Goldstein BH, Mattison JA, Bader K, Graham C, Rettenmaier MA, Brown JV, Markman M. Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer. Gynecol Oncol. 2005 Jan;96(1):132-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Retrospective: Abaid LN, Goldstein BH, Micha JP, Rettenmaier MA, Brown JV 3rd, Markman M. Improved overall survival with 12 cycles of single-agent paclitaxel maintenance therapy following a complete response to induction chemotherapy in advanced ovarian carcinoma. Oncology. 2010;78(5-6):389-93. Epub 2010 Aug 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
B9E-US-S302: Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00191646

Pazopanib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Du Bois et al. 2014 (AGO-OVAR 16)	2009-06 to 2010-08	Phase 3 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 17.9 vs 12.3 mo (HR 0.77, 95% CI 0.64-0.91)

Patients enrolled in AGO-OVAR 16 had histologically confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, were FIGO II to IV, and no evidence of progression after initial treatment.

Preceding treatment

Surgery and at least 5 cycles of first-line platinum and taxane combination chemotherapy

Targeted therapy

Pazopanib (Votrient) 800 mg PO once per day

24-month course

References

AGO-OVAR 16: du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014 Oct 20;32(30):3374-82. Epub 2014 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00866697
1. Subgroup analysis: Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib maintenance therapy in East Asian women with advanced epithelial ovarian cancer: results from AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. link to original article PubMed
2. Update: Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. Epub 2019 Sep 10. link to original article PubMed

Rucaparib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2022 (ATHENA-MONO)	2018-2020	Phase 3 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 20.2 vs 9.2 mo (HR 0.52, 95% CI 0.40-0.68)

Preceding treatment

First-line platinum doublet chemotherapy

Targeted therapy

Rucaparib (Rubraca) 600 mg PO twice per day on days 1 to 28

28-day cycles

References

ATHENA-MONO: Monk BJ, Parkinson C, Lim MC, O'Malley DM, Oaknin A, Wilson MK, Coleman RL, Lorusso D, Bessette P, Ghamande S, Christopoulou A, Provencher D, Prendergast E, Demirkiran F, Mikheeva O, Yeku O, Chudecka-Glaz A, Schenker M, Littell RD, Safra T, Chou HH, Morgan MA, Drochýtek V, Barlin JN, Van Gorp T, Ueland F, Lindahl G, Anderson C, Collins DC, Moore K, Marme F, Westin SN, McNeish IA, Shih D, Lin KK, Goble S, Hume S, Fujiwara K, Kristeleit RS. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022 Dec 1;40(34):3952-3964. Epub 2022 Jun 6. link to original article link to PMC article PubMed NCT03522246

Second-line therapy for relapsed or recurrent disease, platinum-sensitive

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Parmar et al. 2003 (ICON4)	1996-2002	Phase 3 (C)	1a. Carboplatin & Paclitaxel 1b. Cisplatin & Paclitaxel	Seems to have inferior OS
Pfisterer et al. 2006 (AGO-OVAR 2.5)	1999-2002	Phase 3 (C)	Carboplatin & Gemcitabine	Inferior PFS
Alberts et al. 2007 (SWOG S0200)	2002-08 to 2004-12	Phase 3 (C)	Carboplatin & PLD	Did not meet primary endpoint of OS¹

¹Reported efficacy for SWOG S0200 is based on the 2009 update.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1

21-day cycle for 6 to 10 cycles

Regimen variant #2, 300 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bolis et al. 2001 (ARGO 96)	1991 to not reported	Phase 3 (C)	Carboplatin & Epirubicin	Did not meet primary endpoint of ORR

Chemotherapy

Carboplatin (Paraplatin) 300 mg/m² IV once on day 1

28-day cycle for 5 cycles

References

ARGO 96: Bolis G, Scarfone G, Giardina G, Villa A, Mangili G, Melpignano M, Presti M, Tateo S, Franchi M, Parazzini F; Associazione per la Ricerca in Ginecologia Oncologia Study Group. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol. 2001 Apr;81(1):3-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002894
AGO-OVAR 2.5: Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; EORTC GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC-CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00102414
SWOG S0200: Alberts DS, Liu PY, Wilczynski SP, Clouser MC, Lopez AM, Michelin DP, Lanzotti VJ, Markman M; Southwest Oncology Group. Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). Gynecol Oncol. 2008 Jan;108(1):90-4. Epub 2007 Oct 18. link to original article link to PMC article PubMed NCT00043082
1. Update: Markman M, Moon J, Wilczynski S, Lopez AM, Rowland KM Jr, Michelin DP, Lanzotti VJ, Anderson GL, Alberts DS. Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3 randomized trial. Gynecol Oncol. 2010 Mar;116(3):323-5. Epub 2009 Dec 30. link to original article link to PMC article PubMed

Carboplatin & Docetaxel

Regimen variant #1, AUC 2/35, 3 weeks out of 4

Study	Dates of enrollment	Evidence
Kushner et al. 2007	Not reported	Phase 2

Note: BSA was capped at 2 m².

Chemotherapy

Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, given second
Docetaxel (Taxotere) 35 mg/m² (maximum dose of 70 mg) IV over 60 minutes once per day on days 1, 8, 15, given first

Supportive therapy

Dexamethasone (Decadron) 4 mg PO the evening before, the morning of, and evening after docetaxel
5-HT3 antagonist once per day on days 1, 8, 15, prior to chemotherapy
Phenothiazine or 5-HT3 antagonist as needed as an outpatient
Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, immediately prior to docetaxel

28-day cycle for 6 cycles

Regimen variant #2, AUC 5/75

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Strauss et al. 2007	2000-2003	Phase 2
Vergote et al. 2016 (FAR-131)	2009 to not reported	Phase 3 (C)	1a. CP & Farletuzumab; 1.25 mg/kg 1b. DCb & Farletuzumab; 1.25 mg/kg 2a. CP & Farletuzumab; 2.5 mg/kg 2b. DCb & Farletuzumab; 2.5 mg/kg	Did not meet primary endpoint of PFS
Shi et al. 2021 (SOC-1)	2012-2019	Non-randomized part of phase 3 RCT

Note: this is the lower bound of carboplatin dosing specified by FAR-131.

Preceding treatment

SOC-1: Secondary cytoreduction versus no surgical intervention

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1, given second
Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Corticosteroids given twice on day 1; 12 hours and 30 minutes prior to docetaxel
Prophylactic 5-HT3 antagonist

21-day cycle for varying durations: 6 cycles (FAR-131, Strauss et al. 2007); 6 to 9 cycles (SOC-1)

Regimen variant #3, AUC 6/75

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vergote et al. 2016 (FAR-131)	2009 to not reported	Phase 3 (C)	1a. CP & Farletuzumab; 1.25 mg/kg 1b. DCb & Farletuzumab; 1.25 mg/kg 2a. CP & Farletuzumab; 2.5 mg/kg 2b. DCb & Farletuzumab; 2.5 mg/kg	Did not meet primary endpoint of PFS

Note: this is the upper bound of carboplatin dosing specified by FAR-131.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for 6 cycles

References

Strauss HG, Henze A, Teichmann A, Karbe I, Baumgart A, Thomssen C, Koelbl H. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007 Mar;104(3):612-6. Epub 2006 Oct 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Kushner DM, Connor JP, Sanchez F, Volk M, Schink JC, Bailey HH, Harris LS, Stewart SL, Fine J, Hartenbach EM; Wisconsin Oncology Network. Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial. Gynecol Oncol. 2007 May;105(2):358-64. Epub 2007 Jan 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed
FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00849667
SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01611766

Carboplatin & Pegylated liposomal doxorubicin

CD: Carboplatin & Doxil (Pegylated liposomal doxorubicin)
PLDC: Pegylated Liposomal Doxorubicin & Carboplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2010 (CALYPSO)	2005-2007	Phase 3 (E-switch-ic)	Carboplatin & Paclitaxel	Superior PFS (primary endpoint) Median PFS: 11.3 vs 9.4 mo (HR 0.82, 95% CI 0.72-0.94)
Sehouli et al. 2016 (HECTOR)	2007-2009	Randomized Phase 2 (C)	Carboplatin & Topotecan	Did not meet primary endpoint of PFS12
Colombo et al. 2023 (INOVATYON)	2011-12 to 2017-09-18	Phase 3 (C)	PLD & Trabectedin	Did not meet primary endpoint of OS
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (C)	1a. Carboplatin, PLD, Bevacizumab 1b. Carboplatin, Gemcitabine, Bevacizumab 1c. CP & Bevacizumab	Inferior PFS
Liu et al. 2022 (NRG-GY004)	2016-02-04 to 2017-11-13	Phase 3 (C)	1. Olaparib 2. Cediranib & Olaparib	Did not meet primary endpoint of PFS

Note: CALYPSO stands for Caelyx (Pegylated liposomal doxorubicin) in Platinum Sensitive Ovarian patients

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV once on day 1

Supportive therapy

"Antiemetics, including a serotonin 5-HT3 antagonist and corticosteroid"

28-day cycle for varying durations: 4 or more cycles, depending on response and toxicity; 6 cycles (MITO 16); 6 or more cycles (CALYPSO, INOVATYON); indefinitely (HECTOR, NRG-GY004)

References

CALYPSO: Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00189553
1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00437307
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802749
NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT02446600
INOVATYON: Colombo N, Fossati R, Gadducci A, Bologna A, Sehouli J, Rulli E, Maenpaa J, Berger R, Sessa C, Montes A, Ottevanger NB, Vergote I, D'Incalci M, Chekerov R, Nyvang GB, Riniker S, Herbertson R, Barretina-Ginesta MP, Deryal M, Mirza MR, Biagioli E, Iglesias M, Funari G, Romeo M, Churruca Galaz C, Tasca G, Pardo B, Tognon G, Rubio-Perez MJ, DeCensi A, De Giorgi U, Zola P, Benedetti Panici P, Aglietta M, Arcangeli V, Zamagni C, Westermann A, Heinzelmann-Schwarz V, Tsibulak I, Wimberger P, Poveda A. INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line. Br J Cancer. 2023 Apr;128(8):1503-1513. Epub 2023 Feb 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01379989

Carboplatin, Pegylated liposomal doxorubicin, Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18)	2013-2015	Phase 3 (E-switch-ic)	Carboplatin, Gemcitabine, Bevacizumab	Seems to have superior PFS (primary endpoint) Median PFS: 13.3 vs 11.6 mo (HR 0.81, 95% CI 0.68-0.96)
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (E-esc)	1a. Carboplatin & PLD 1b. Carboplatin & Gemcitabine 1c. CP	Superior PFS (primary endpoint) Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65)
Kurtz et al. 2023 (ATALANTE)	2016-09-28 to 2019-10-04	Phase 3 (C)	1a. GCb, Atezolizumab, Bevacizumab 1b. CP, Atezolizumab, Bevacizumab 1c. Carboplatin, PLD, Atezolizumab, Bevacizumab	Might have inferior PFS (co-primary endpoint)

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
Pegylated liposomal doxorubicin (Doxil) as follows:
- Cycles 1 to 6: 30 mg/m² IV once on day 1

Targeted therapy

Bevacizumab (Avastin) as follows:
- Cycles 1 to 6: 10 mg/kg IV once per day on days 1 & 15
- Cycle 7 onwards: 15 mg/kg IV once on day 1

28-day cycle for 6 cycles, then 21-day cycles

References

AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01837251
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802749
ATALANTE: Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02891824

Carboplatin & Gemcitabine (GCb)

GCb: Gemcitabine & Carboplatin

Regimen variant #1, limited duration

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pfisterer et al. 2006 (AGO-OVAR 2.5)	1999-2002	Phase 3 (E-RT-esc)	Carboplatin	Superior PFS (primary endpoint) Median PFS: 8.6 vs 5.8 mo (HR 0.72, 95% CI 0.58-0.90)
Aghajanian et al. 2012 (OCEANS)	2007-2010	Phase 3 (C)	Carboplatin, Gemcitabine, Bevacizumab	Inferior PFS
Coleman et al. 2017 (NRG/GOG-0213)	2007-2011	Non-randomized part of phase 3 RCT
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (C)	1a. Carboplatin, PLD, Bevacizumab 1b. Carboplatin, Gemcitabine, Bevacizumab 1c. CP & Bevacizumab	Inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 4 IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

21-day cycle for varying durations: 6 cycles (MITO 16); 6 to 10 cycles (AGO-OVAR 2.5, OCEANS)

Regimen variant #2, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sehouli et al. 2016 (HECTOR)	2007-2009	Randomized Phase 2 (C)	Carboplatin & Topotecan	Did not meet primary endpoint of PFS12
Liu et al. 2022 (NRG-GY004)	2016-02-04 to 2017-11-13	Phase 3 (C)	1. Olaparib 2. Cediranib & Olaparib	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 4 IV over 30 to 60 minutes once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8

21-day cycles

References

AGO-OVAR 2.5: Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; EORTC GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC-CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00102414
OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00434642
1. Update: Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. Epub 2015 Aug 10. link to original article link to PMC article PubMed
HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00437307
NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00565851
1. Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802749
NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT02446600

Carboplatin & Gemcitabine (GCb) & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Aghajanian et al. 2012 (OCEANS)	2007-2010	Phase 3 (E-RT-esc)	GCb	Superior PFS (primary endpoint) Median PFS: 12.4 vs 8.4 mo (HR 0.48, 95% CI 0.39-0.61) Did not meet secondary endpoint of OS¹ Median OS: 33.6 vs 32.9 mo (HR 0.95, 95% CI 0.77-1.18)
Coleman et al. 2017 (NRG/GOG-0213)	2007-2011	Non-randomized part of phase 3 RCT
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18)	2013-2015	Phase 3 (C)	Carboplatin, Doxil, Bevaciuzmab	Seems to have inferior PFS
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (E-esc)	1a. Carboplatin & PLD 1b. Carboplatin & Gemcitabine 1c. CP	Superior PFS (primary endpoint) Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65)
Kurtz et al. 2023 (ATALANTE)	2016-09-28 to 2019-10-04	Phase 3 (C)	1a. GCb, Atezolizumab, Bevacizumab 1b. CP, Atezolizumab, Bevacizumab 1c. Carboplatin, PLD, Atezolizumab, Bevacizumab	Might have inferior PFS (co-primary endpoint)

¹Reported efficacy for OS in OCEANS is based on the 2015 update.

Chemotherapy

Carboplatin (Paraplatin) AUC 4 IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1, given first

21-day cycle for varying durations: 6 cycles (AGO-OVAR 2.21/ENGOT-ov 18, ATALANTE, MITO 16, NRG/GOG-0213); 6 to 10 cycles (OCEANS)

Subsequent treatment

Bevacizumab maintenance

References

OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00434642
1. Update: Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. Epub 2015 Aug 10. link to original article link to PMC article PubMed
NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00565851
1. Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01837251
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802749
ATALANTE: Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02891824

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin

Regimen variant #1, AUC 5/175, limited duration

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Coleman et al. 2017 (NRG/GOG-0213)	2007-2011	Phase 3 (C)	Carboplatin, Paclitaxel, Bevacizumab	Might have inferior OS
Vergote et al. 2019 (OAS 07OVA)	2009-2013	Phase 3 (C)	Carboplatin & Paclitaxel micellar	Non-inferior PFS
Pignata et al. 2017 (MITO-8)	2009-2015	Phase 3 (C)	Investigator's choice¹ of: 1a. PLD 1b. Topotecan 1c. Gemcitabine	Did not meet primary endpoint of OS
Vergote et al. 2016 (FAR-131)	2009 to not reported	Phase 3 (C)	1a. CP & Farletuzumab; 1.25 mg/kg 1b. DCb & Farletuzumab; 1.25 mg/kg 2a. CP & Farletuzumab; 2.5 mg/kg 2b. DCb & Farletuzumab; 2.5 mg/kg	Did not meet primary endpoint of PFS
Oza et al. 2014 (D0810C00041)	2010-02-12 to 2010-07-30	Randomized Phase 2 (C)	CP & Olaparib	Inferior PFS
Shi et al. 2021 (SOC-1)	2012-2019	Non-randomized part of phase 3 RCT
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (C)	1a. Carboplatin, PLD, Bevacizumab 1b. Carboplatin, Gemcitabine, Bevacizumab 1c. CP & Bevacizumab	Inferior PFS

¹Initially PLD was the only option. After an amendment in 2012, topotecan, gemcitabine, or "any other drug approved in this setting" were allowed.

Preceding treatment

SOC-1: Secondary cytoreduction versus no surgical intervention

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

Supportive therapy

(varies depending on reference):
Corticosteroids and prophylactic 5-HT3 antagonist
Premedication (with steroids & antihistamines) prior to paclitaxel

21-day cycle for varying durations: 6 cycles (D0810C00041, FAR-131, MITO 16); 6 to 8 cycles (NRG/GOG-0213); 6 to 9 cycles (SOC-1)

Subsequent treatment

MITO-8, upon progression: Third-line non-platinum-based chemotherapy (NPBC)

Regimen variant #2, AUC 5/175, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Parmar et al. 2003 (ICON4)	1996-2002	Phase 3 (E-esc)	1a. Carboplatin 1b. Cisplatin	Seems to have superior OS Median OS: 29 vs 24 mo (HR 0.82, 95% CI 0.69-0.97)
Pujade-Lauraine et al. 2010 (CALYPSO)	2005-2007	Phase 3 (C)	Carboplatin & PLD	Inferior PFS
Sehouli et al. 2016 (HECTOR)	2007-2009	Randomized Phase 2 (C)	Carboplatin & Topotecan	Did not meet primary endpoint of PFS12
Liu et al. 2022 (NRG-GY004)	2016-02-04 to 2017-11-13	Phase 3 (C)	1. Olaparib 2. Cediranib & Olaparib	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive therapy

(varies depending on reference):
Corticosteroids and prophylactic 5-HT3 antagonist
Premedication (with steroids & antihistamines) prior to paclitaxel

21-day cycles

Regimen variant #3, AUC 6/175, limited duration

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vergote et al. 2019 (OAS 07OVA)	2009-2013	Phase 3 (C)	Carboplatin & Paclitaxel micellar	Non-inferior PFS
Vergote et al. 2016 (FAR-131)	2009 to not reported	Phase 3 (C)	1a. CP & Farletuzumab; 1.25 mg/kg 1b. DCb & Farletuzumab; 1.25 mg/kg 2a. CP & Farletuzumab; 2.5 mg/kg 2b. DCb & Farletuzumab; 2.5 mg/kg	Did not meet primary endpoint of PFS
Oza et al. 2014 (D0810C00041)	2010-02-12 to 2010-07-30	Randomized Phase 2 (C)	CP & Olaparib	Inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for 6 cycles

Regimen variant #4, AUC 6/175, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Liu et al. 2022 (NRG-GY004)	2016-02-04 to 2017-11-13	Phase 3 (C)	1. Olaparib 2. Cediranib & Olaparib	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 to 60 minutes once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive therapy

(varies depending on reference):
Corticosteroids and prophylactic 5-HT3 antagonist
Premedication (with steroids & antihistamines) prior to paclitaxel

21-day cycles

References

ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002894
CALYPSO: Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00189553
1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
D0810C00041: Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01081951
FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00849667
HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00437307
NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00565851
MITO-8: Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U, Lorusso D, Murgia V, Sorio R, Ferrandina G, Sacco C, Cormio G, Breda E, Cinieri S, Natale D, Mangili G, Pisano C, Cecere SC, Di Napoli M, Salutari V, Raspagliesi F, Arenare L, Bergamini A, Bryce J, Daniele G, Piccirillo MC, Gallo C, Perrone F. Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study. J Clin Oncol. 2017 Oct 10;35(29):3347-3353. Epub 2017 Aug 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00657878
OAS 07OVA: Vergote I, Bergfeldt K, Franquet A, Lisyanskaya AS, Bjermo H, Heldring N, Buyse M, Brize A. A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel. Gynecol Oncol. 2020 Feb;156(2):293-300. Epub 2019 Dec 9. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00989131
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802749
SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01611766
NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT02446600

Carboplatin & Paclitaxel (CP) & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Coleman et al. 2017 (NRG/GOG-0213)	2007-2011	Phase 3 (E-RT-esc)	Carboplatin & Paclitaxel	Might have superior OS (primary endpoint) Median OS: 42.2 vs 37.3 mo (HR 0.83, 95% CI 0.68-1.005)
Pignata et al. 2021 (MITO 16)	2013-2016	Phase 3 (E-esc)	1a. Carboplatin & PLD 1b. Carboplatin & Gemcitabine 1c. CP	Superior PFS (primary endpoint) Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65)
Kurtz et al. 2023 (ATALANTE)	2016-09-28 to 2019-10-04	Phase 3 (C)	1a. GCb, Atezolizumab, Bevacizumab 1b. CP, Atezolizumab, Bevacizumab 1c. Carboplatin, PLD, Atezolizumab, Bevacizumab	Might have inferior PFS (co-primary endpoint)

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 up to 8: AUC 5 IV over 60 minutes once on day 1, given third
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 up to 8: 175 mg/m² IV over 3 hours once on day 1, given first

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV over 90 minutes once on day 1, given second
- If tolerated, infusion time is reduced to 60 minutes with cycle 2, and 30 minutes with cycle 3 onwards

21-day cycles

References

NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00565851
MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01802749
ATALANTE: Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed

Carboplatin & Paclitaxel (CP) & Olaparib

CP & Olaparib: Carboplatin, Paclitaxel, Olaparib

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oza et al. 2014 (D0810C00041)	2010-02-12 to 2010-07-30	Randomized Phase 2 (E-esc)	Carboplatin & Paclitaxel	Superior PFS (primary endpoint) Median PFS: 12.2 vs 9.6 mo (HR 0.51, 95% CI 0.34-0.77)

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 4 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV once on day 1

Targeted therapy

Olaparib (Lynparza) as follows:
- Cycles 1 to 6: 200 mg PO twice per day on days 1 to 10
- Cycle 7 onwards: 400 mg PO twice per day on days 1 to 21

21-day cycles

References

D0810C00041: Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01081951

Cisplatin & Gemcitabine (GC)

Regimen

Study	Dates of enrollment	Evidence
Rose et al. 2003c	Not reported	Phase 2

Chemotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1 & 8, given second
Gemcitabine (Gemzar) 750 mg/m² IV over 30 minutes once per day on days 1 & 8, given first

Supportive therapy

5-HT3 antagonists
Corticosteroids
Prochlorperazine (Compazine)
Magnesium supplementation with cisplatin

21-day cycles

References

Rose PG, Mossbruger K, Fusco N, Smrekar M, Eaton S, Rodriguez M. Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma. Gynecol Oncol. 2003 Jan;88(1):17-21. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Cisplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Parmar et al. 2003 (ICON4)	1996-2002	Phase 3 (E-esc)	1a. Carboplatin 1b. Cisplatin	Seems to have superior OS Median OS: 29 vs 24 mo (HR 0.82, 95% CI 0.69-0.97)

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycles

References

ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002894

Etoposide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Rose et al. 1998	1992-1995	Phase 2	ORR: 34%

Chemotherapy

Etoposide (Vepesid) by the following exposure-based criteria:
- No prior pelvic radiation: 50 mg/m² PO once per day on days 1 to 21
- Previous pelvic radiation: 30 mg/m² PO once per day on days 1 to 21

28-day cycles

Dose and schedule modifications

In patients with previous pelvic radiation, etoposide dose could be increased up to 50 mg/m² depending on toxicity

References

Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article dosing details in manuscript have been reviewed by our editors PubMed

nab-Paclitaxel monotherapy

Regimen

Study	Dates of enrollment	Evidence
Teneriello et al. 2009	2005-2006	Phase 2

Chemotherapy

Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m² IV over 30 minutes once on day 1

21-day cycle for 6 to 8 cycles

References

Teneriello MG, Tseng PC, Crozier M, Encarnacion C, Hancock K, Messing MJ, Boehm KA, Williams A, Asmar L. Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009 Mar 20;27(9):1426-31. Epub 2009 Feb 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ROSELLA: NCT05257408

Relapsed or recurrent disease, platinum-resistant

Altretamine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Markman et al. 1998	Not reported	Phase 2

Note: there is not enough information in the FDA label to determine for sure whether this is one of the registration trials; it is representative of many phase 2 trials of this agent.

Chemotherapy

Altretamine (Hexalen) 260 mg/m² PO once per day on days 1 to 14

28-day cycles

References

Markman M, Blessing JA, Moore D, Ball H, Lentz SS; Gynecologic Oncology Group. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 1998 Jun;69(3):226-9. link to original article PubMed

Bevacizumab monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study	Dates of enrollment	Evidence
Burger et al. 2007	2002-2004	Phase 2
Cannistra et al. 2007	2005	Phase 2

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles

References

Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI; Gynecologic Oncology Group. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Nov 20;25(33):5165-71. Erratum in: J Clin Oncol. 2014 Nov 10;32(32):3686. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007 Nov 20;25(33):5180-6. Erratum in: J Clin Oncol. 2008 Apr 1;26(10):1773. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Docetaxel monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study	Dates of enrollment	Evidence
Rose et al. 2003a	1998-06 to 2000-01	Phase 2

Chemotherapy

Docetaxel (Taxotere) 100 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
Diphenhydramine (Benadryl) 50 mg IV once on day 1, immediately prior to docetaxel
Antiemetics as needed

21-day cycles

References

Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH; Gynecologic Oncology Group. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Feb;88(2):130-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Etoposide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Rose et al. 1998	1992-1995	Phase 2	ORR: 27%

Chemotherapy

Etoposide (Vepesid) by the following exposure-based criteria:
- No prior pelvic radiation: 50 mg/m² PO once per day on days 1 to 21
- Previous pelvic radiation: 30 mg/m² PO once per day on days 1 to 21

28-day cycles

Dose and schedule modifications

In patients with previous pelvic radiation, etoposide dose could be increased up to 50 mg/m² depending on toxicity

References

Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Gemcitabine monotherapy

Regimen variant #1, 2 weeks out of 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Mutch et al. 2007 (B9E-US-S301)	2002-2004	Phase 3 (E-switch-ic)	PLD	Did not meet primary endpoint of PFS
Kurzeder et al. 2016 (PENELOPE)	2013-10-02 to 2014-09-18	Phase 3 (C)	1a. Gemcitabine & Pertuzumab 1b. Paclitaxel & Pertuzumab 1c. Topotecan & Pertuzumab	Did not meet primary endpoint of PFS

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8

21-day cycles

Regimen variant #2, 3 weeks out of 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ferrandina et al. 2008 (MITO-3)	2003-2007	Phase 3 (E-switch-ic)	PLD	Might have superior ORR (secondary endpoint)
Lheureux et al. 2021 (PHL-093)	2014-2018	Phase 3 (C)	Adavosertib & Gemcitabine	Inferior PFS
Hamanishi et al. 2021 (NINJA)	2015-10-07 to 2017-12-21	Phase 3 (C)	Nivolumab	Did not meet primary endpoint of OS Median OS: 12.1 vs 10.1 mo (HR 1.00, 95% CI 0.77-1.25)
Awaiting publication (NItCHE)	2020-ongoing	Phase 3 (C)	Niraparib & Dostarlimab	TBD if different primary endpoint of OS

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycles

References

B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00191607
MITO-3: Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01684878
1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
PHL-093: Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02101775
NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed JapicCTI-153004
NItCHE: NCT04679064

Gemcitabine & Pegylated liposomal doxorubicin

Regimen

Study	Dates of enrollment	Evidence
Ferrandina et al. 2005	2000-12 to 2004-01	Phase 2

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Metoclopramide (Reglan) once per day on days 1 & 8, prior to chemotherapy

21-day cycles

References

Ferrandina G, Paris I, Ludovisi M, D'Agostino G, Testa A, Lorusso D, Zanghi M, Pisconti S, Pezzella G, Adamo V, Breda E, Scambia G. Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol. 2005 Aug;98(2):267-73. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Mirvetuximab soravtansine monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Moore et al. 2021 (FORWARD I)	2017-01-24 to 2018-04-23	Phase 3 (E-RT-switch-ooc)	Physician's choice of: 1a. Paclitaxel 1b. Pegylated liposomal doxorubicin 1c. Topotecan	Did not meet primary endpoint of PFS Median PFS: 4.1 vs 4.4 mo (HR 0.98, 95% CI 0.73-1.31)
Moore et al. 2023 (MIRASOL)	2020-02-03 to NR	Phase 3 (E-switch-ooc)	Physician's choice of: 1a. Paclitaxel 1b. Pegylated liposomal doxorubicin 1c. Topotecan	Superior OS (secondary endpoint) Median OS: 16.46 vs 12.75 mo (HR 0.67, 95% CI 0.50-0.89) Superior PFS (primary endpoint) RMPFS12: 6.13 vs 4.72 mo
Matulonis et al. 2023 (SORAYA)	2020-06 to 2021-05	Non-randomized (RT)

Biomarker eligibility criteria

High folate receptor-alpha expression

Antibody-drug conjugate therapy

Mirvetuximab soravtansine (Elahere) 6 mg/kg (based on adjusted ideal body weight) IV once on day 1

21-day cycles

References

FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02631876
SORAYA: Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. Epub 2023 Jan 30. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT04296890
MIRASOL: Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04209855

Paclitaxel monotherapy

Regimen variant #1, 80 mg/m² 3 out of 4 weeks

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pignata et al. 2015 (MITO 11)	2010-2013	Randomized Phase 2 (C)	Paclitaxel & Pazopanib	Inferior PFS
Moore et al. 2021 (FORWARD I)	2017-01-24 to 2018-04-23	Phase 3 (C)	Mirvetuximab soravtansine	Did not meet primary endpoint of PFS
Awaiting publication (NItCHE)	2020-ongoing	Phase 3 (C)	Niraparib & Dostarlimab	TBD if different primary endpoint of OS

Biomarker eligibility criteria

FORWARD I: High folate receptor-alpha expression

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, 80 mg/m² weekly

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Markman et al. 2006	Not reported	Phase 2
Lindemann et al. 2017 (Ovaresist)	2002-2007	Phase 3 (C)	Tamoxifen	Superior PFS¹
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (C)	1a. Paclitaxel & Bevacizumab 1b. PLD & Bevacizumab 1c. Topotecan & Bevacizumab	Inferior PFS
Monk et al. 2014 (TRINOVA-1)	2010-2012	Phase 3 (C)	Paclitaxel & Trebananib	Inferior PFS
Kurzeder et al. 2016 (PENELOPE)	2013-10-02 to 2014-09-18	Phase 3 (C)	1a. Gemcitabine & Pertuzumab 1b. Paclitaxel & Pertuzumab 1c. Topotecan & Pertuzumab	Did not meet primary endpoint of PFS
Arend et al. 2023 (OVAL)	2017-12 to 2022-03	Phase 3 (C)	Ofra-vec	Did not meet co-primary endpoints of PFS/OS
Moore et al. 2023 (MIRASOL)	2020-02-03 to NR	Phase 3 (C)	Mirvetuximab soravtansine	Inferior OS

¹Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.
Note: PENELOPE reported giving paclitaxel on days 1, 8, 15 of a 21-day cycle, which is identical to the schedule below.

Biomarker eligibility criteria

MIRASOL: High folate receptor-alpha expression

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Dexamethasone (Decadron) 10 mg IV or PO once on day 1; 30 to 60 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 25 to 50 mg IV once on day 1; 30 to 60 minutes prior to paclitaxel
H2 blocker once on day 1; 30 to 60 minutes prior to paclitaxel

7-day cycles

Regimen variant #3, 175 mg/m², q3wk, 3-hour infusion

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Eisenhauer et al. 1994	1991-07-23 to 1992-03-06	Phase 3 (E-RT-esc)	Paclitaxel; 135 mg/m²	Did not meet primary endpoint of ORR Seems to have superior PFS (secondary endpoint)
Gore et al. 1995	1992-1993	Non-randomized
ten Bokkel Huinink et al. 1997	Not reported	Phase 3 (C)	Topotecan	Might have inferior TTP¹
Cantù et al. 1999	1992-1995	Phase 3 (E-de-esc)	CAP	Seems to have inferior OS
Buda et al. 2004	1994-1999	Phase 3 (C)	Epirubicin & Paclitaxel	Did not meet primary endpoint of OS
Awaiting publication (DOXIL-CAN-301)	1997-2000	Phase 3 (C)	PLD	Not available²

¹Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.
²DOXIL-CAN-301 appears to have been published in abstract form only, in 2002; this abstract is no longer available.

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycles

Regimen variant #4, 175 mg/m², q3wk, 24-hour infusion

Historic variant

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Omura et al. 2003	1992-1995	Phase 3 (C)	Paclitaxel; 250 mg/m²	Seems to have inferior ORR

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV continuous infusion over 24 hours, started on day 1

21-day cycles

Regimen variant #5, 200 mg/m², q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rosenberg et al. 2002	1995-1998	Phase 3 (C)	Paclitaxel; weekly 67 mg/m²	Did not meet primary endpoint of ORR

Chemotherapy

Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1

21-day cycles

Regimen variant #6, with range

Historic variant

Study	Dates of enrollment	Evidence
McGuire et al. 1989	Not reported	Phase 2
Kohn et al. 1994	1991-01-01 to 1992-04-01	Phase 2

Chemotherapy

Paclitaxel (Taxol)

References

McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989 Aug 15;111(4):273-9. link to original article PubMed
Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N, Bacon M, Santabarbara P, Onetto N, Winograd B, Canetta R. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994 Dec;12(12):2654-66. link to original article dosing details in abstract have been reviewed by our editors PubMed
Kohn EC, Sarosy G, Bicher A, Link C, Christian M, Steinberg SM, Rothenberg M, Adamo DO, Davis P, Ognibene FP, Cunnion RE, Reed E. Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst. 1994 Jan 5;86(1):18-24. link to original article PubMed
Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H, Thompson JM. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer. 1995 Oct;72(4):1016-9. link to original article link to PMC article PubMed
ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. link to original article dosing details in manuscript have been reviewed by our editors PubMed
1. Update: ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. link to original article PubMed
Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. link to original article PubMed
Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, Parö G. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta Oncol. 2002;41(5):418-24. link to original article PubMed
Omura GA, Brady MF, Look KY, Averette HE, Delmore JE, Long HJ, Wadler S, Spiegel G, Arbuck SG. Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: an intergroup study. J Clin Oncol. 2003 Aug 1;21(15):2843-8. Epub 2003 Jun 13. link to original article dosing details in abstract have been reviewed by our editors PubMed
Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C; GONO. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, GONO (Gruppo Oncologico Nord Ovest) group and IOR (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004 Jun 1;90(11):2112-7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S; Gynecologic Oncology Group. Phase II trial of weekly paclitaxel (80 mg/m²) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jun;101(3):436-40. Epub 2005 Dec 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed
AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
TRINOVA-1: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 Jul;15(8):799-808. Epub 2014 Jun 17. link to original article PubMed NCT01204749
1. Update: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Ma H, Vogl FD, Bach BA, Oza AM. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol. 2016 Oct;143(1):27-34. Epub 2016 Aug 18. link to original article PubMed
MITO 11: Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01644825
PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01684878
1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
Ovaresist: Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02728622
FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02631876
OVAL: Arend RC, Monk BJ, Shapira-Frommer R, Haggerty AF, Alvarez EA, Amit A, Alvarez Secord A, Muller C, Casado Herraez A, Herzog TJ, Tewari KS, Cohen JG, Huang M, Yachnin A, Holeman LL, Ledermann JA, Rachmilewitz Minei T, Buyse M, Fain Shmueli S, Lavi M, Harats D, Penson RT; OVAL/GOG-3018 Investigators. Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018). J Clin Oncol. 2024 Jan 10;42(2):170-179. Epub 2023 Oct 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03398655
MIRASOL: Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04209855
AGO-OVAR 2.29: NCT03353831
DOXIL-CAN-301: NCT00653952
EPIK-O: NCT04729387
GOG-3059: NCT04729608
NItCHE: NCT04679064

Paclitaxel & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (E-RT-esc)	1a. Paclitaxel 1b. PLD 1c. Topotecan	Superior PFS (primary endpoint) Median PFS: 6.7 vs 3.4 mo (HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15, 22

Targeted therapy

Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15

28-day cycles

References

AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
NItCHE: NCT04679064

Paclitaxel & Pazopanib

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pignata et al. 2015 (MITO 11)	2010-2013	Randomized Phase 2 (E-esc)	Paclitaxel	Superior PFS (primary endpoint) Median PFS: 6.35 vs 3.49 mo (HR 0.42, 95% CI 0.25-0.69)

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

Targeted therapy

Pazopanib (Votrient) 800 mg PO once per day on days 1 to 28, taken at least 2 hours after or 1 hour before eating

28-day cycles

References

MITO 11: Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01644825

Pazopanib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Friedlander et al. 2010	Not reported	Phase 2

Targeted therapy

Pazopanib (Votrient) 800 mg PO once per day on days 1 to 28

28-day cycles

References

Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, Ma B, Hodge JP, Lager JJ. A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010 Oct;119(1):32-7. Epub 2010 Jun 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Pegylated liposomal doxorubicin monotherapy

Regimen variant #1, 40 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lindemann et al. 2017 (Ovaresist)	2002-2007	Phase 3 (C)	Tamoxifen	Superior PFS
Ferrandina et al. 2008 (MITO-3)	2003-2007	Phase 3 (E-switch-ic)	Gemcitabine	Might have inferior ORR (secondary endpoint)
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (C)	1a. Paclitaxel & Bevacizumab 1b. PLD & Bevacizumab 1c. Topotecan & Bevacizumab	Inferior PFS
Motohashi et al. 2020 (JGOG 3018)	2010-2017	Phase 3 (E-de-esc)	PLD; 50 mg/m²	Inconclusive whether non-inferior PFS (primary endpoint)
Pujade-Lauraine et al. 2021 (JAVELIN Ovarian 200)	2016-01-05 to 2017-05-16	Phase 3 (C)	1. Avelumab 2. PLD & Avelumab	Did not meet co-primary endpoints of PFS/OS
Moore et al. 2021 (FORWARD I)	2017-01-24 to 2018-04-23	Phase 3 (C)	Mirvetuximab soravtansine	Did not meet primary endpoint of PFS
Moore et al. 2023 (MIRASOL)	2020-02-03 to NR	Phase 3 (C)	Mirvetuximab soravtansine	Inferior OS
Awaiting publication (NItCHE)	2020-ongoing	Phase 3 (C)	Niraparib & Dostarlimab	TBD if different primary endpoint of OS

Note: Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.

Biomarker eligibility criteria

FORWARD I & MIRASOL: High folate receptor-alpha expression

Chemotherapy

Pegylated liposomal doxorubicin (Doxil) 40 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Methylprednisolone (Solumedrol) 20 mg IV once on day 1; 30 minutes prior to pegylated liposomal doxorubicin

28-day cycles

Regimen variant #2, 50 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Muggia et al. 1997	1994-1995	Phase 2 (RT)
Gordon et al. 2000	Not reported-1998	Phase 2 (RT)
Gordon et al. 2001 (Doxil Study 30-49)	1997-1999	Phase 3 (E-RT-switch-ic)	Topotecan	Might have superior PFS (co-primary endpoint)
Mutch et al. 2007 (B9E-US-S301)	2002-2004	Phase 3 (C)	Gemcitabine	Did not meet primary endpoint of PFS
Vergote et al. 2009 (ASSIST-1)	2003-2006	Phase 3 (C)	Canfosfamide	Superior OS
Awaiting publication (ASSIST-3)	2004-2008	Phase 3 (C)	Canfosfamide & Carboplatin	Did not meet primary endpoint of PFS
Monk et al. 2010 (OVA-301)	2005-2007	Phase 3 (C)	PLD & Trabectedin	Might have inferior OS¹
Colombo et al. 2012 (CEPO906A2303)	2005-2009	Phase 3 (C)	Patupilone	Did not meet primary endpoint of OS
Vergote et al. 2010 (ASSIST-5)	2006-09 to 2007-06	Phase 3 (C)	Canfosfamide & PLD	Did not meet primary endpoint of PFS
Motohashi et al. 2020 (JGOG 3018)	2010-2017	Phase 3 (C)	PLD; 40 mg/m²	Inconclusive whether non-inferior PFS
Marth et al. 2016 (TRINOVA-2)	2011-2013	Phase 3 (C)	PLD & Trebananib	Did not meet primary endpoint of PFS Median PFS: 7.2 vs 7.6 mo (HR 1.09, 95% CI 0.81-1.47)
Monk et al. 2020 (CR100983)	2013-2018	Phase 3 (C)	PLD & Trabectedin	Did not meet primary endpoint of OS Median OS: 22.2 vs 23.8 mo (HR 1.09, 95% CI 0.85-1.37)
Gaillard et al. 2021 (CORAIL)	2015-06-26 to 2018-10-12	Phase 3 (C)	Lurbinectedin	Did not meet primary endpoint of PFS Median PFS: 3.6 vs 3.5 mo (HR 0.95)
Hamanishi et al. 2021 (NINJA)	2015-10-07 to 2017-12-21	Phase 3 (C)	Nivolumab	Did not meet primary endpoint of OS Median OS: 12.1 vs 10.1 mo (HR 1.00, 95% CI 0.77-1.25)

¹Reported efficacy for OVA-301 is based on the 2012 update.

Chemotherapy

Pegylated liposomal doxorubicin (Doxil) 50 mg/m² IV over 60 to 90 minutes once on day 1

28-day cycles

References

Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang LJ. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987-93. link to original article PubMed
Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Rosales R, Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3093-100. link to original article dosing details in abstract have been reviewed by our editors PubMed
Doxil Study 30-49: Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
1. Update: Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org NCT00191607
MITO-3: Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ASSIST-1: Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Kavanagh J, Vermorken JB, Meng L, Jones M, Brown G, Kaye S; ASSIST-1 Study Group. Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. Eur J Cancer. 2009 Sep;45(13):2324-32. Epub 2009 Jun 8. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00057720
ASSIST-5: Vergote I, Finkler NJ, Hall JB, Melnyk O, Edwards RP, Jones M, Keck JG, Meng L, Brown GL, Rankin EM, Burke JJ, Boccia RV, Runowicz CD, Rose PG. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2010 Jul;20(5):772-80. link to original article PubMed NCT00350948
OVA-301: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00113607
1. PRO analysis: Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. link to original article PubMed
2. Update: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed
CEPO906A2303: Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, Scambia G, Engelholm SA, Joly F, Weber D, El-Hashimy M, Li J, Souami F, Wing P, Engelholm S, Bamias A, Schwartz P. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. J Clin Oncol. 2012 Nov 1;30(31):3841-7. Epub 2012 Sep 17. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00262990
AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
TRINOVA-2: Marth C, Vergote I, Scambia G, Oberaigner W, Clamp A, Berger R, Kurzeder C, Colombo N, Vuylsteke P, Lorusso D, Hall M, Renard V, Pignata S, Kristeleit R, Altintas S, Rustin G, Wenham RM, Mirza MR, Fong PC, Oza A, Monk BJ, Ma H, Vogl FD, Bach BA. ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer. Eur J Cancer. 2017 Jan;70:111-121. Epub 2016 Dec 1. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01281254
Ovaresist: Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02728622
CR100983: Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. Epub 2020 Jan 8. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01846611
JGOG 3018: Motohashi T, Yabuno A, Michimae H, Ohishi T, Nonaka M, Takano M, Nishio S, Fujiwara H, Fujiwara K, Kondo E, Sugiyama T, Tabata T. Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial. J Gynecol Oncol. 2021 Jan;32(1):e9. Epub 2020 Nov 10. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed UMIN000003130
FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02631876
JAVELIN Ovarian 200: Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, Richardson GE, Sessa C, Yonemori K, Banerjee S, Leary A, Tinker AV, Jung KH, Madry R, Park SY, Anderson CK, Zohren F, Stewart RA, Wei C, Dychter SS, Monk BJ. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021 Jul;22(7):1034-1046. Epub 2021 Jun 15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02580058
NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed JapicCTI-153004
CORAIL: Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02421588
MIRASOL: Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04209855
AGO-OVAR 2.29: NCT03353831
ARTISTRY-7: NCT05092360
ASSIST-3: NCT00102973
EPIK-O: NCT04729387
NItCHE: NCT04679064
PROCEED_OV: NCT01170650

Pegylated liposomal doxorubicin & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (E-RT-esc)	1a. Paclitaxel 1b. PLD 1c. Topotecan	Superior PFS (primary endpoint) Median PFS: 6.7 vs 3.4 mo (HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Pegylated liposomal doxorubicin (Doxil) 40 mg/m² IV once on day 1

Targeted therapy

Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15

28-day cycles

References

AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
NItCHE: NCT04679064

Pegylated liposomal doxorubicin & Trabectedin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2010 (OVA-301)	2005-2007	Phase 3 (E-esc)	PLD	Seems to have superior PFS (primary endpoint) Median PFS: 7.3 vs 5.8 mo (HR 0.79, 95% CI 0.65-0.96) Might have superior OS¹ (secondary endpoint) Median OS: 22.2 vs 18.9 mo (HR 0.86, 95% CI 0.72-1.02)

¹Reported efficacy is based on the 2012 update.

Chemotherapy

Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV over 90 minutes once on day 1, given first
Trabectedin (Yondelis) 1.1 mg/m² IV over 3 hours once on day 1, given second, 30 minutes later

21-day cycles

References

OVA-301: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00113607
1. PRO analysis: Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. link to original article PubMed
2. Update: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed

Pemetrexed monotherapy

Regimen variant #1, 700 mg/m²

Study	Dates of enrollment	Evidence
Miller et al. 2009 (GOG-0126Q)	2004-2006	Phase 2

Note: this is the dosage for patients with previous radiation therapy.

Chemotherapy

Pemetrexed (Alimta) 700 mg/m² IV over 10 minutes once on day 1

Supportive therapy

Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed

21-day cycles

Regimen variant #2, 900 mg/m²

Study	Dates of enrollment	Evidence
Miller et al. 2009 (GOG-0126Q)	2004-2006	Phase 2

Chemotherapy

Pemetrexed (Alimta) 900 mg/m² IV over 10 minutes once on day 1

Supportive therapy

Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed

21-day cycles

References

GOG-0126Q: Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH; Gynecologic Oncology Group. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009 Jun 1;27(16):2686-91. Epub 2009 Mar 30. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00087087

Topotecan monotherapy

Regimen variant #1, 4 mg/m², 3 weeks out of 4 x 12 mo

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sehouli et al. 2010 (TOWER_ov)	2005-2008	Randomized Phase 2 (E-switch-ic)	Topotecan; q3wk	Did not meet primary endpoint of CBR
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (C)	1a. Paclitaxel & Bevacizumab 1b. PLD & Bevacizumab 1c. Topotecan & Bevacizumab	Inferior PFS

Note: TOWER should not be confused with the trial by the same name in B-ALL.

Chemotherapy

Topotecan (Hycamtin) 4 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycle for up to 13 cycles (1 year)

Regimen variant #2, 4 mg/m², 3 weeks out of 4, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (C)	1a. Paclitaxel & Bevacizumab 1b. PLD & Bevacizumab 1c. Topotecan & Bevacizumab	Inferior PFS
Moore et al. 2021 (FORWARD I)	2017-01-24 to 2018-04-23	Phase 3 (C)	Mirvetuximab soravtansine	Did not meet primary endpoint of PFS
Moore et al. 2023 (MIRASOL)	2020-02-03 to NR	Phase 3 (C)	Mirvetuximab soravtansine	Inferior OS

Biomarker eligibility criteria

FORWARD I & MIRASOL: High folate receptor-alpha expression

Chemotherapy

Topotecan (Hycamtin) 4 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #3, 6.25 mg/m², split dosing, q3wk x 12 mo

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sehouli et al. 2010 (TOWER_ov)	2005-2008	Randomized Phase 2 (C)	Topotecan; weekly	Did not meet primary endpoint of CBR

Note: TOWER should not be confused with the trial by the same name in B-ALL.

Chemotherapy

Topotecan (Hycamtin) 1.25 mg/m² IV over 30 minutes once per day on days 1 to 5

21-day cycle for up to 18 cycles (1 year)

Regimen variant #4, 6.25 mg/m², split dosing, q3wk, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sehouli et al. 2008	1999-2004	Phase 3 (C)	1. Etoposide & Topotecan 2. Gemcitabine & Topotecan	Did not meet primary endpoint of OS
Meier et al. 2009 (AGO-OVAR 2.3)	1998-2002	Phase 3 (E-switch-ic)	Treosulfan	Superior OS
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (C)	1a. Paclitaxel & Bevacizumab 1b. PLD & Bevacizumab 1c. Topotecan & Bevacizumab	Inferior PFS
Kurzeder et al. 2016 (PENELOPE)	2013-10-02 to 2014-09-18	Phase 3 (C)	1a. Gemcitabine & Pertuzumab 1b. Paclitaxel & Pertuzumab 1c. Topotecan & Pertuzumab	Did not meet primary endpoint of PFS
Moore et al. 2021 (FORWARD I)	2017-01-24 to 2018-04-23	Phase 3 (C)	Mirvetuximab soravtansine	Did not meet primary endpoint of PFS
Moore et al. 2023 (MIRASOL)	2020-02-03 to NR	Phase 3 (C)	Mirvetuximab soravtansine	Inferior OS
Awaiting publication (NItCHE)	2020-ongoing	Phase 3 (C)	Niraparib & Dostarlimab	TBD if different primary endpoint of OS

Note: this was the dosing used in third-line therapy in AGO-OVAR 2.3.

Biomarker eligibility criteria

FORWARD I & MIRASOL: High folate receptor-alpha expression

Chemotherapy

Topotecan (Hycamtin) 1.25 mg/m² IV over 30 minutes once per day on days 1 to 5

21-day cycles

Regimen variant #5, 7.5 mg/m², split dosing, q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bookman et al. 1996	Not reported	Phase 2 (RT)
ten Bokkel Huinink et al. 1997	Not reported	Randomized (E-RT-switch-ic)	Paclitaxel	Might have superior TTP¹ (co-primary endpoint)
Gordon et al. 2001 (Doxil Study 30-49)	1997-1999	Phase 3 (C)	PLD	Might have inferior PFS
Meier et al. 2009 (AGO-OVAR 2.3)	1998-2002	Phase 3 (E-switch-ic)	Treosulfan	Superior OS
Gaillard et al. 2021 (CORAIL)	2015-06-26 to 2018-10-12	Phase 3 (C)	Lurbinectedin	Did not meet primary endpoint of PFS Median PFS: 3.6 vs 3.5 mo (HR 0.95)

¹Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.
Note: this was the dosing used in second-line therapy in AGO-OVAR 2.3.

Chemotherapy

Topotecan (Hycamtin) 1.5 mg/m² IV over 30 minutes once per day on days 1 to 5

21-day cycles

References

Bookman MA, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs JB, Fields SZ. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol. 1998 Oct;16(10):3345-52. link to original article PubMed
ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. link to original article dosing details in manuscript have been reviewed by our editors PubMed
1. Update: ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. link to original article PubMed
Doxil Study 30-49: Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
1. Update: Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2008 Jul 1;26(19):3176-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
AGO-OVAR 2.3: Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. link to original article dosing details in supplement have been reviewed by our editors PubMed
TOWER: Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, Markmann S, Mahner S, Mueller L, Lorenz R, Nugent A, Wilke J, Kuznik A, Doering G, Wischnik A, Sommer H, Meerpohl HG, Schroeder W, Lichtenegger W, Oskay-Oezcelik G; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2011 Jan 10;29(2):242-8. Epub 2010 Nov 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00170677
AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01684878
1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02631876
CORAIL: Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02421588
MIRASOL: Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04209855
DOXILOVC3001: NCT01840943
NItCHE: NCT04679064

Topotecan & Bevacizumab

Regimen variant #1, topotecan 3 weeks out of 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (E-RT-esc)	1a. Paclitaxel 1b. PLD 1c. Topotecan	Superior PFS (primary endpoint) Median PFS: 6.7 vs 3.4 mo (HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Topotecan (Hycamtin) 4 mg/m² IV once per day on days 1, 8, 15

Targeted therapy

Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15

28-day cycles

Regimen variant #2, topotecan 6.25 mg/m², split dosing, q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)	2009-2011	Phase 3 (E-RT-esc)	1a. Paclitaxel 1b. PLD 1c. Topotecan	Superior PFS (primary endpoint) Median PFS: 6.7 vs 3.4 mo (HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Topotecan (Hycamtin) 1.25 mg/m² IV once per day on days 1 to 5

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles

References

AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976911
1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. link to original article link to PMC article PubMed
2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
NItCHE: NCT04679064

Trabectedin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Krasner et al. 2007	2002-2004	Phase 2

Chemotherapy

Trabectedin (Yondelis) 0.58 mg/m² IV over 3 hours once per day on days 1, 8, 15

Supportive therapy

Dexamethasone (Decadron) 10 mg IV once per day on days 1, 8, 15, given 30 minutes prior to chemotherapy

28-day cycles

References

Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, Provencher DM, Campos S, Gore ME. A phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007 Dec 17;97(12):1618-24. Epub 2007 Nov 13. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed

Treosulfan monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Meier et al. 2009 (AGO-OVAR 2.3)	1998-2002	Phase 3 (E-switch-ic)	Topotecan	Inferior OS
Sehouli et al. 2016	2002-2014	Phase 3b (C)	Treosulfan; PO	Might have superior OS

Chemotherapy

Treosulfan (Ovastat) by the following renal function-based criteria:
- CrCl more than 40 mL/min/1.73 m²: 7000 mg/m² IV once on day 1
- CrCl 20 to 40 mL/min/1.73 m²: 6000 mg/m² IV once on day 1
- CrCl less than 20 mL/min/1.73 m²: 5000 mg/m² IV once on day 1

28-day cycles

References

AGO-OVAR 2.3: Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. link to original article dosing details in supplement have been reviewed by our editors PubMed
Sehouli J, Tomè O, Dimitrova D, Camara O, Runnebaum IB, Tessen HW, Rautenberg B, Chekerov R, Muallem MZ, Lux MP, Trarbach T, Gitsch G. A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO). J Cancer Res Clin Oncol. 2017 Mar;143(3):541-550. Epub 2016 Nov 28. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed

Vinorelbine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Rothenberg et al. 2004	1995-03 to 1997-07	Phase 2

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1 & 8

21-day cycles

References

Rothenberg ML, Liu PY, Wilczynski S, Nahhas WA, Winakur GL, Jiang CS, Moinpour CM, Lyons B, Weiss GR, Essell JH, Smith HO, Markman M, Alberts DS; SWOG. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004 Dec;95(3):506-12. link to original article dosing details in abstract have been reviewed by our editors PubMed

@@ Line 1: / Line 1: @@
-'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|gyn}}
+''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Ovarian_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Ovarian cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
+<br>'''This page contains regimens which were not tested in biomarker-specific or histology-specific populations.
+<br>'''The following links will take you to biomarker-specific subpages:'''
+*Regimens for [[Ovarian cancer, HRD-positive|'''HRD-positive ovarian cancer are here''']].
+'''The following links will take you to histology-specific subpages:'''
+*Regimens for [[Low-grade serous ovarian cancer|'''low-grade serous ovarian cancer (LGSOC) are here''']].
+{| class="wikitable sortable" style="float:right; margin-right: 5px;"
+|-
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
+|}
 {{TOC limit|limit=3}}
+=Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
+==[https://www.asco.org/ ASCO]==
+*'''2022:''' Tew et al. [https://doi.org/10.1200/jco.22.01934 Poly(ADP-Ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update] [https://pubmed.ncbi.nlm.nih.gov/36150092 PubMed]
+**'''2020:''' Tew et al. [https://doi.org/10.1200/jco.20.01924 PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942301/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32790492 PubMed]
+*'''2021:''' Vanderpuye et al. [https://doi.org/10.1200/go.21.00085 Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34185571 PubMed]
+*'''2020:''' Konstantinopoulos et al. [https://doi.org/10.1200/jco.19.02960 Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31986064 PubMed]
+*'''2016:''' Wright et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5512594/ Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/27502591/ PubMed]
-=Primary chemotherapy for advanced/metastatic disease=
+==[https://www.esmo.org/ ESMO]==
-==Carboplatin & Docetaxel==
+*'''2023:''' González-Martín et al. [https://doi.org/10.1016/j.annonc.2023.07.011 Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/37597580/ PubMed]
-===Regimen, Vasey et al. 2004===
+**'''2013:''' Ledermann et al. [https://doi.org/10.1093/annonc/mdt333 Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/24078660/ PubMed]
-Level of Evidence:
+**'''2010:''' Colombo et al. [https://doi.org/10.1093/annonc/mdq244 Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555088/ PubMed]
-<span
+**'''2009:''' Aebi & Castiglione. [https://doi.org/10.1093/annonc/mdp117 Newly and relapsed epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454452/ PubMed]
-style="background:#00CD00;
+**'''2008:''' Aebi & Castiglione. [https://doi.org/10.1093/annonc/mdn073 Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456751/ PubMed]
-padding:3px 6px 3px 6px;
+**'''2007:''' Vasey. [https://doi.org/10.1093/annonc/mdm017 Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491026/ PubMed]
-border-color:black;
+**'''2005:''' Vasey et al. [https://doi.org/10.1093/annonc/mdi823 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of epithelial ovarian carcinoma] [https://pubmed.ncbi.nlm.nih.gov/15888736/ PubMed]
-border-width:2px;
+*'''2018:''' Ray-Coquard et al. [https://doi.org/10.1093/annonc/mdy001 Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/29697741/ PubMed]
-border-style:solid;">Phase III</span>
+**'''2012:''' Colombo et al. [https://doi.org/10.1093/annonc/mds223 Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/22997450/ PubMed]
+**'''2009:''' Colombo et al. [https://doi.org/10.1093/annonc/mdp118 Non-epithelial ovarian cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454453/ PubMed]
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 1 hour once on day 1, given second
+==[https://www.esmo.org/ ESMO]/[https://www.esgo.org/ ESGO]/ESP==
-*[[Docetaxel (Taxotere)]] 75 mg/m2 IV over 1 hour once on day 1, given first
+*'''2024:''' Ledermann et al. [https://doi.org/10.1016/j.annonc.2023.11.015 ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease] [https://pubmed.ncbi.nlm.nih.gov/38307807/ PubMed]
+**'''2019:''' Colombo et al. [https://doi.org/10.1093/annonc/mdz062 ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease] [https://pubmed.ncbi.nlm.nih.gov/31046081 PubMed]
-'''21-day cycles x 6 cycles'''
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453 NCCN Guidelines - Ovarian Cancer, Including Fallopian Tube Cancer and Primary Peritoneal Cancer]
+**'''2021:''' Armstrong et al. [https://doi.org/10.6004/Jnccn.2021.0007 Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/33545690/ PubMed]
+**'''2016:''' Morgan et al. [https://doi.org/10.6004/jnccn.2016.0122 Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/27587625/ PubMed]
+**'''2013:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2013.0142 Ovarian cancer, version 2.2013.] [https://pubmed.ncbi.nlm.nih.gov/24142821/ PubMed]
+**'''2012:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2012.0140 Ovarian cancer, version 3.2012.] [https://pubmed.ncbi.nlm.nih.gov/23138163/ PubMed]
+**'''2011:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2011.0008 Epithelial ovarian cancer.] [https://pubmed.ncbi.nlm.nih.gov/21233246/ PubMed]
+**'''2008:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2008.0058 Ovarian cancer. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/18926089/ PubMed]
+**'''2006:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2006.0076 Ovarian cancer. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17020669/ PubMed]
+**'''2004:''' Morgan et al. [https://doi.org/10.6004/Jnccn.2004.0044 Ovarian cancer clinical practice guidelines.] [https://pubmed.ncbi.nlm.nih.gov/19780297/ PubMed]
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1435 NCCN Guidelines - Genetic/Familial High-Risk Assessment: Breast and Ovarian]
-Supportive medications:
+==[https://www.sgo.org/ SGO]/[https://www.asco.org/ ASCO]==
-*[[Dexamethasone (Decadron)]] 8 mg PO BID the day before, the day of, and day after docetaxel
+*'''2016:''' Wright et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512594/ Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/27650684 PubMed]
-*Ondansetron (Zofran) 8 mg or Granisetron (Kytril) 3 mg for [[antiemesis]]
+=Adjuvant therapy for early stage disease=
+==Carboplatin monotherapy {{#subobject:4a42d8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, AUC 5 {{#subobject:18269c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/jnci/95.2.125 Colombo et al. 2003 (ICON1)]
+|1991-2000
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Ovarian_cancer_-_null_regimens#Observation|Observation]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>OS60: 82% vs 74%<br>(HR 0.67, 95% CI 0.50-0.90)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2003 pooled update.''<br>
+''Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper).''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Ovarian_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 350 mg/m<sup>2</sup> {{#subobject:17262c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/jnci/95.2.113 Trimbos et al. 2003 (ACTION)]
+|1990-2000
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Ovarian_cancer_-_null_regimens#Observation|Observation]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>OS60: 82% vs 74%<br>(HR 0.67, 95% CI 0.50-0.90)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2003 pooled update.''<br>
+''Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper). Cycle length was not specified in the paper; 21-day cycle is typical for this drug.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Ovarian_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 350 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 4 to 6 cycles (see note)'''
+</div></div>
+===References===
+# '''ACTION:''' Trimbos JB, Vergote I, Bolis G, Vermorken JB, Mangioni C, Madronal C, Franchi M, Tateo S, Zanetta G, Scarfone G, Giurgea L, Timmers P, Coens C, Pecorelli S; [[Study_Groups#EORTC|EORTC]]-ACTION collaborators. Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst. 2003 Jan 15;95(2):113-25. [https://doi.org/10.1093/jnci/95.2.113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12529344/ PubMed]
+## '''Pooled update:''' Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; [[Study_Groups#EORTC|EORTC]] Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. [https://doi.org/10.1093/jnci/95.2.105 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12529343/ PubMed]
+# '''ICON1:''' Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, Torri V, Williams C, Lissoni A, Bonazzi C; ICON. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst. 2003 Jan 15;95(2):125-32. [https://doi.org/10.1093/jnci/95.2.125 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12529345/ PubMed] [https://clinicaltrials.gov/study/NCT00002477 NCT00002477]
+## '''Pooled update:''' Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; [[Study_Groups#EORTC|EORTC]] Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. [https://doi.org/10.1093/jnci/95.2.105 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12529343/ PubMed]
+==Carboplatin & Paclitaxel (CP) {{#subobject:cdf21c|Regimen=1}}==
+CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 6/175 {{#subobject:841asdf|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110746/ Mannel et al. 2011 (GOG-0175)]
+|1998-2006
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Ovarian_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Ovarian_cancer_-_null_regimens#Observation|Observation]] versus [[#Paclitaxel_monotherapy_999|Paclitaxel]] maintenance
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 7.5/175 {{#subobject:841d9f|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2006.06.013 Bell et al. 2006 (GOG 157)]
+|1995-1998
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]] x 6
+| style="background-color:#ffffbf" |Did not meet primary endpoint of RR
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Ovarian_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 7.5 IV over 30 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+# '''GOG 157:''' Bell J, Brady MF, Young RC, Lage J, Walker JL, Look KY, Rose GS, Spirtos NM; Gynecologic Oncology Group. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Sep;102(3):432-9. Epub 2006 Jul 24. [https://doi.org/10.1016/j.ygyno.2006.06.013 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16860852/ PubMed]
+# '''GOG-0175:''' Mannel RS, Brady MF, Kohn EC, Hanjani P, Hiura M, Lee R, Degeest K, Cohn DE, Monk BJ, Michael H. A randomized phase III trial of IV carboplatin and paclitaxel x 3 courses followed by observation versus weekly maintenance low-dose paclitaxel in patients with early-stage ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jul;122(1):89-94. Epub 2011 May 6. [https://doi.org/10.1016/j.ygyno.2011.03.013 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110746/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21529904/ PubMed] [https://clinicaltrials.gov/study/NCT00003644 NCT00003644]
+=Neoadjuvant chemotherapy for advanced stage disease=
+==Carboplatin & Paclitaxel (CP) {{#subobject:ab0654|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, AUC 5/175 x 3 {{#subobject:68d2cb|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(14)62223-6 Kehoe et al. 2015 (CHORUS)]
+|2004-2010
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]]
+|style="background-color:#eeee01"|Non-inferior OS (primary endpoint)<br>Median OS: 24.1 vs 22.6 mo<br>(HR 0.87, 95% CI 0.72-1.05)
+|-
+|}
+''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Interval_debulking_surgery|Interval debulking surgery]], then adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]] x 3
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, AUC 5/175 x 6 {{#subobject:d2168a|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Dates of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1016/j.ejca.2016.01.017 Fagotti et al. 2016 (SCORPION)]
+|2011-2014
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#1a9850" |Superior QoL
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Interval_debulking_surgery|Interval debulking surgery]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, AUC 6/175 x 3 {{#subobject:f05e45|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa0908806 Vergote et al. 2010 (EORTC 55971)]
+|1998-2006
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]]
+|style="background-color:#eeee01"|Non-inferior OS (primary endpoint)<br>Median OS: 30 vs 29 mo<br>(HR 0.98, 90% CI 0.84-1.13)
+|-
+|[https://doi.org/10.1016/S0140-6736(14)62223-6 Kehoe et al. 2015 (CHORUS)]
+|2004-2010
+|style="background-color:#1a9851"|Phase 3 (C)
+|Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]]
+|style="background-color:#eeee01"|Non-inferior OS
+|-
+|}
+''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Interval_debulking_surgery|Interval debulking surgery]], then adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|CP]] x 3
+</div></div>
 ===References===
-# Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. [http://jnci.oxfordjournals.org/content/96/22/1682.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15547181 PubMed]
+# '''EORTC 55971:''' Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; [[Study_Groups#EORTC|EORTC]]-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. [https://doi.org/10.1056/NEJMoa0908806 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20818904/ PubMed] [https://clinicaltrials.gov/study/NCT00003636 NCT00003636]
+# '''CHORUS:''' Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. Epub 2015 May 19. [https://doi.org/10.1016/S0140-6736(14)62223-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26002111/ PubMed] ISRCTN74802813
+# '''SCORPION:''' Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. Epub 2016 Mar 19. [https://doi.org/10.1016/j.ejca.2016.01.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26998845/ PubMed] [https://clinicaltrials.gov/study/NCT01461850 NCT01461850]
+=First-line chemotherapy for advanced stage disease=
+''Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.''
+==Carboplatin monotherapy {{#subobject:4f85d8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, AUC 5 {{#subobject:07553c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Dates of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1016/S0140-6736(98)04119-1 Parmar et al. 1998 (ICON2)]
+|1991-1996
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|[[Ovarian_cancer_-_historical#CISCA|CAP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Less toxic
+|-
+|[https://doi.org/10.1016/s0140-6736(02)09738-6 Parmar et al. 2002 (ICON3)]
+|1995-1998
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Ovarian_cancer_-_historical#CISCA|CAP]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, AUC 6, q3wk {{#subobject:8672ea|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s0140-6736(02)09738-6 Parmar et al. 2002 (ICON3)]
+|1995-1998
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Ovarian_cancer_-_historical#CISCA|CAP]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669851/ Banerjee et al. 2012 (SCOTROC 4)]
+|2004-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_monotherapy_2|Carboplatin]]; dose-escalated
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, AUC 6, q4wk {{#subobject:9e367c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1998.16.7.2426 Gore et al. 1998]
+|1987-1995
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_monotherapy_2|Carboplatin]]; AUC 12 x 4
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS24
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+'''28-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, AUC 9 {{#subobject:9e174c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2001.19.4.1001 Markman et al. 2001 (GOG 114)]
+|1992-1995
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Complex_multipart_regimens#GOG_114|See link]]
+| style="background-color:#91cf60" |[[Complex_multipart_regimens#GOG_114|See link]]
+|-
+|}
+''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with optimal debulking
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 9 IV once on day 1
+'''28-day cycle for 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Adjuvant [[#Cisplatin_.26_Paclitaxel_2|IP Cisplatin & IV Paclitaxel]] x 6
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #5, 400 mg/m<sup>2</sup>, q4wk {{#subobject:68b7cd|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#f01e2c"
+|<small><span style="color:white;">'''Historic variant'''</span></small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1994.12.10.2066 Taylor et al. 1994]
+|1981-10 to 1984-06
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Ovarian_cancer_-_historical#Cisplatin_monotherapy|Cisplatin]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1093/jnci/81.19.1464 Mangioni et al. 1989]
+|1985-01 to 1987-02
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Ovarian_cancer_-_historical#Cisplatin_monotherapy|Cisplatin]]
+| style="background-color:#ffffbf" |Did not meet endpoint
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for 10 cycles'''
+</div></div>
-==Carboplatin & Doxorubicin liposomal==
+===References===
-===Regimen, Pignata et al. 2006 (MITO-2)===
+# Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. [https://doi.org/10.1093/jnci/81.19.1464 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2674459/ PubMed]
-Level of Evidence:
+# Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. [https://doi.org/10.1200/JCO.1994.12.10.2066 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7931475/ PubMed]
-<span
+# Gore M, Mainwaring P, A'Hern R, MacFarlane V, Slevin M, Harper P, Osborne R, Mansi J, Blake P, Wiltshaw E, Shepherd J; London Gynaecological Oncology Group. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. J Clin Oncol. 1998 Jul;16(7):2426-34. [https://doi.org/10.1200/JCO.1998.16.7.2426 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9667260/ PubMed]
-style="background:#00CD00;
+# '''ICON2:''' Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. [https://doi.org/10.1016/S0140-6736(98)04119-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9843101/ PubMed]
-padding:3px 6px 3px 6px;
+# '''GOG 114:''' Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://doi.org/10.1200/JCO.2001.19.4.1001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11181662/ PubMed]
-border-color:black;
+# '''ICON3:''' Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. [https://doi.org/10.1016/s0140-6736(02)09738-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12241653/ PubMed]
-border-width:2px;
+# '''SCOTROC 4:''' Banerjee S, Rustin G, Paul J, Williams C, Pledge S, Gabra H, Skailes G, Lamont A, Hindley A, Goss G, Gilby E, Hogg M, Harper P, Kipps E, Lewsley LA, Hall M, Vasey P, Kaye SB; GCIG. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG. Ann Oncol. 2013 Mar;24(3):679-87. Epub 2012 Oct 5. [https://doi.org/10.1093/annonc/mds494 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669851/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23041585/ PubMed] [https://clinicaltrials.gov/study/NCT00098878 NCT00098878]
-border-style:solid;">Phase III</span>
+==Carboplatin & Docetaxel {{#subobject:1113e0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-''Eligibility criteria for Pignata et al. 2006 & Pignata et al. 2011 included: "a cytologic or histologic diagnosis of epithelial ovarian cancer (stage IC to IV according to International Federation of Gynecology and Obstetrics staging system).''
+===Regimen {{#subobject:e5c1b0|Variant=1}}===
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, given first
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV over 60 minutes once on day 1, given second
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-'''21-day cycles x 3 to 6 cycles;''' all patients received 3 cycles of therapy.  Patients with stable or responsive disease received an additional 3 cycles.
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
-Supportive medications (per Pignata et al. 2006):
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/jnci/djh323 Vasey et al. 2004 (SCOTROC-1)]
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO twice per day the day before, the day of, and day after docetaxel
+*ONE of the following 5-HT3 antagonists:
+**[[Ondansetron (Zofran)]] 8 mg
+**[[Granisetron]] 3 mg
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+# '''SCOTROC-1:''' Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. [https://doi.org/10.1093/jnci/djh323 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15547181/ PubMed] [https://clinicaltrials.gov/study/NCT00003998 NCT00003998]
+==Carboplatin & Pegylated liposomal doxorubicin {{#subobject:8a720d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:c48aad|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ Pignata et al. 2006 (MITO-2)]
+|2003-2007
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+''Eligibility criteria for MITO-2 included: "a cytologic or histologic diagnosis of epithelial ovarian cancer (stage IC to IV according to International Federation of Gynecology and Obstetrics staging system).''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given first'''
+*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
+====Supportive therapy====
 *"No prophylactic use of G-CSF was recommended. Therapeutic and prophylactic use of G-CSF was allowed for febrile or afebrile grade 4 neutropenia."
+'''21-day cycle for 3 to 6 cycles'''
+''All patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.''
+</div></div>
 ===References===
-# Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO Investigators. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16882344 PubMed]
+# '''MITO-2:''' Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. [https://doi.org/10.1186/1471-2407-6-202 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16882344/ PubMed] [https://clinicaltrials.gov/study/NCT00326456 NCT00326456]
-# '''Update:''' Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. doi: 10.1200/JCO.2010.33.8566. Epub 2011 Aug 15. [http://jco.ascopubs.org/content/29/27/3628.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21844495 PubMed]
+## '''Update:''' Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. Epub 2011 Aug 15. [https://doi.org/10.1200/jco.2010.33.8566 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21844495/ PubMed]
+==Carboplatin & Gemcitabine (GCb) {{#subobject:65ad86|Regimen=1}}==
-==Carboplatin & Gemcitabine==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen, Gordon et al. 2011===
+===Regimen {{#subobject:dd8477|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1016/j.ygyno.2011.08.018 Gordon et al. 2011 (B9E-US-S302)]
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, given second
+|2002-2006
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV 30 minutes once per day on days 1 & 8, given first
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
-'''21-day cycles x up to 6 cycles; patients with complete response could optionally proceed to receive consolidation'''
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
-====Consolidation====
+|}
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV once on day 1
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-'''28-day cycles x up to 12 cycles'''
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given second'''
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given first'''
+'''21-day cycle for up to 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*B9E-US-S302, patients with CR: optional [[#Paclitaxel_monotherapy|paclitaxel]] consolidation
+</div></div>
 ===References===
-# Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. [http://www.sciencedirect.com/science/article/pii/S0090825811007037 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21978765 PubMed]
+# '''B9E-US-S302:''' Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. [https://doi.org/10.1016/j.ygyno.2011.08.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21978765/ PubMed] [https://clinicaltrials.gov/study/NCT00191646 NCT00191646]
+==Carboplatin & Paclitaxel (CP) {{#subobject:dd35ee|Regimen=1}}==
-==Carboplatin & Paclitaxel==
+TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin
-===Regimen #1, Ozols et al. 2003===
+<br>PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen variant #1, q1wk AUC 2/60 {{#subobject:1b495c|Variant=1}}===
-style="background:#00CD00;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Study
-border-color:black;
+!style="width: 20%"|Dates of enrollment
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Carboplatin (Paraplatin)]] AUC 7.5 IV once on day 1
+|-
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+|[https://doi.org/10.1016/S1470-2045(14)70049-X Pignata et al. 2014 (MITO-7)]
+|2008-2012
-'''21-day cycles x 6 cycles'''
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q3wk AUC 6/175
-Supportive medications:
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
-*[[Dexamethasone (Decadron)]] 20 mg PO given twice, at 12 and 6 hours prior to chemotherapy OR 20 mg IV once 30 minutes prior to paclitaxel
+|-
-*Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to paclitaxel
+|}
-*Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to paclitaxel
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-===Regimen #2, Vasey et al. 2004 & Pignata et al. 2006 (MITO-2)===
+*[[Carboplatin (Paraplatin)]] AUC 2 IV once on day 1
-Level of Evidence:
+*[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV once on day 1
-<span
+'''7-day cycle for 18 cycles'''
-style="background:#00CD00;
+</div></div><br>
-padding:3px 6px 3px 6px;
+<div class="toccolours" style="background-color:#eeeeee">
-border-color:black;
+===Regimen variant #2, q3wk AUC 5, q1wk 80 {{#subobject:d267gua|Variant=1}}===
-border-width:2px;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 1 hour once on day 1, given second
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-**Pignata et al. 2011 (MITO-2) gave carboplatin over 30 minutes
+!style="width: 20%"|Comparator
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1, given first
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-'''21-day cycles x 6 cycles;''' in Pignata et al. 2011 (MITO-2), all patients received 3 cycles of therapy.  Patients with stable or responsive disease received an additional 3 cycles.
+|[https://doi.org/10.1016/s1470-2045(21)00342-9 Monk et al. 2021 (JAVELIN Ovarian 100)]
+|2016-2018
-Supportive medications (per Vasey et al. 2004):
+|style="background-color:#1a9851"|Phase 3 (C)
-*[[Dexamethasone (Decadron)]] 20 mg PO given twice, at 12 and 6 hours prior to paclitaxel
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Avelumab_999|CP & Avelumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_then_Avelumab_999|CP, then Avelumab]]
-*Diphenhydramine (Benadryl) 50 mg IV or chlorpheniramine 10 mg IV once 30 minutes prior to paclitaxel
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
-*Ranitidine (Zantac) 50 mg IV or Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to paclitaxel
+|-
-*Ondansetron (Zofran) 8 mg or Granisetron (Kytril) 3 mg for [[antiemesis]]
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
-===Regimen #3, Katsumata et al. 2009===
+====Chemotherapy====
-Level of Evidence:
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
-<span
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-style="background:#00CD00;
+'''21-day cycle for 6 cycles'''
-padding:3px 6px 3px 6px;
+</div></div><br>
-border-color:black;
+<div class="toccolours" style="background-color:#eeeeee">
-border-width:2px;
+===Regimen variant #3, q3wk AUC 5/175 {{#subobject:7ef902|Variant=1}}===
-border-style:solid;">Phase III</span>
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 1 hour once on day 1
+!style="width: 15%"|Dates of enrollment
-*[[Paclitaxel (Taxol)]] 180 mg/m2 IV over 3 hours once on day 1
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
-'''21-day cycles x 6 to 9 cycles, depending on response'''
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-Supportive medications:
+|-
+|[https://doi.org/10.1200/JCO.2000.18.17.3084 Neijt et al. 2000]
+|1994-1997
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1200/JCO.2005.03.2938 du Bois et al. 2006 (AGO-OVAR 5)]
+|1997-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#TEC|TEC]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|
+|-
+|[https://doi.org/10.1093/jnci/djh323 Vasey et al. 2004 (SCOTROC-1)]
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1200/JCO.2006.09.7527 Möbus et al. 2007 (HIDOC-EIS)]
+|1998-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|High-dose chemotherapy with auto HSCT
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1093/annonc/mds060 Lindemann et al. 2012 (EORTC 55981)]
+|1999-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#TEC|TEC]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1093/jnci/djq362 Hoskins et al. 2010 (EORTC 55012)]
+|2001-2005
+|style="background-color:#1a9851"|Phase 3 (C)
+|Cisplatin & Topotecan, then [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#1a9850" |Less toxic
+|-
+|[https://doi.org/10.1200/JCO.2009.27.4696 du Bois et al. 2010 (AGO-OVAR 9)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#TCG|TCG]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ Pignata et al. 2006 (MITO-2)]
+|2003-2007
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Pegylated_liposomal_doxorubicin|Carboplatin & PLD]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00366-6 du Bois et al. 2015 (AGO-OVAR 12)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nintedanib|TC & Nintedanib]]
+|style="background-color:#fc8d59"|Seems to have inferior PFS
+|
+|-
+|[https://doi.org/10.1016/j.ejca.2016.01.017 Fagotti et al. 2016 (SCORPION)]
+|2011-2014
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|TC]]; neoadjuvant
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#d73027" |Inferior QoL
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902268/ Clamp et al. 2019 (ICON8)]
+|2011-2014
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q1wk AUC 2/80<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q3wk AUC 6, q1wk 80 ("dose-dense")
+|style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS
+|
+|-
+|[https://doi.org/10.1016/S1470-2045(19)30178-0 Vergote et al. 2019 (TRINOVA-3)]
+|2012-2014
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trebananib|TC & Trebananib]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00342-9 Monk et al. 2021 (JAVELIN Ovarian 100)]
+|2016-2018
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Avelumab_999|CP & Avelumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_then_Avelumab_999|CP, then Avelumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|
+|-
+|}
+''Note: In MITO-2, all patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*Neijt et al. 2000: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]] was recommended
+*SCOTROC-1, MITO-2, AGO-OVAR 12, SCORPION: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Supportive therapy====
+*(per Vasey et al. 2004):
+*[[Dexamethasone (Decadron)]] 20 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel
+*One of the following antihistamines:
+**[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+**[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IV once on day 1; 30 minutes prior to paclitaxel
+*One of the following H2-blockers
+**[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+**[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+*One of the following serotonin 5-HT3 antagonists:
+**[[Ondansetron (Zofran)]] 8 mg
+**[[Granisetron]] 3 mg
+'''21-day cycle for 6 or more cycles (see note)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, q3wk AUC 6, q1wk 80 {{#subobject:d2604f|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(09)61157-0 Katsumata et al. 2009 (JGOG 3016)]
+|2003-2005
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q3wk AUC 6/180
+|style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>OS36: 72.1% vs 65.1%<br>(HR 0.75, 95% CI 0.57-0.98)<br><br>Superior PFS (primary endpoint)<br>Median PFS: 28 vs 17.2 mo<br>(HR 0.71, 95% CI 0.58-0.88)
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6941439/ Coleman et al. 2019 (VELIA)]
+|rowspan=2|2015-2017
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib|CP & Veliparib]] x 6
+|style="background-color:#d3d3d3"|Not reported
+|-
+|2. [[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib|CP & Veliparib]] x 6, then [[#Veliparib_monotherapy_777|Veliparib maint.]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00342-9 Monk et al. 2021 (JAVELIN Ovarian 100)]
+|2016-2018
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Avelumab_999|CP & Avelumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_then_Avelumab_999|CP, then Avelumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1056/EVIDoa2200225 Nagao et al. 2023 (iPocc)]
+|2010-05 to 2016-08
+|style="background-color:#1a9851"|Phase 2/3 (C)
+|[[#IP_Carboplatin_.26_Paclitaxel|IP Carboplatin & Paclitaxel]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+====Supportive therapy====
 *"Standard premedication"
+'''21-day cycle for 6 to 9 cycles, depending on response and protocol'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #4, Katsumata et al. 2009 (dose-dense paclitaxel)===
+===Regimen variant #5, q3wk AUC 6/175 {{#subobject:92b591|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1200/JCO.2007.14.9807 Lhommé et al. 2008]
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 1 hour once on day 1
+|1997-1999
-*[[Paclitaxel (Taxol)]] 80 mg/m2 IV over 1 hour once per day on days 1, 8, 15
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Paclitaxel_.26_Valspodar_999|Paclitaxel & Valspodar]]
-'''21-day cycles x 6 to 9 cycles, depending on response'''
+|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
+|-
+|[https://doi.org/10.1056/NEJMoa0908806 Vergote et al. 2010 (EORTC 55971)]
+|1998-2006
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|TC]] x 3, then interval debulking, then [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]] x 3
+|style="background-color:#eeee01"|Non-inferior OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2011.08.018 Gordon et al. 2011 (B9E-US-S302)]
+|2002-2006
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668552/ Bookman et al. 2009 (ICON5)]
+|2001-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Stub#TCG|TCG]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pegylated_liposomal_doxorubicin_999|TC & PLD]]<br> 3. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Topotecan_999|TC & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2008.01.005 Alberts et al. 2008 (GRACES)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Interferon_gamma-1b_999|CP & IFN gamma-1b]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|rowspan=2|[https://doi.org/10.1056/NEJMoa1104390 Burger et al. 2011 (GOG-0218)]
+|rowspan=2|2005-2009
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|TC & Bevacizumab]] x 6
+| style="background-color:#fee08b" |Might have inferior PFS
+|-
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|TC & Bevacizumab]] x 22
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1056/NEJMoa1103799 Perren et al. 2011 (ICON7)]
+|2006-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|Carboplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS<sup>1</sup>
+|-
+|[https://doi.org/10.1200/jco.2016.66.9010 Sugiyama et al. 2016 (JGOG3017/GCIG)]
+|2006-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Irinotecan_999|Cisplatin & Irinotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/S1470-2045(14)70049-X Pignata et al. 2014 (MITO-7)]
+|2008-2012
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q1wk AUC 2/60
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00366-6 du Bois et al. 2015 (AGO-OVAR 12)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nintedanib|TC & Nintedanib]]
+|style="background-color:#fc8d59"|Seems to have inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ Chan et al. 2016 (GOG-0262)]
+|2010-2012
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; dose-dense
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902268/ Clamp et al. 2019 (ICON8)]
+|2011-2014
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q1wk AUC 2/80<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; q3wk AUC 6, q1wk 80 ("dose-dense")
+|style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS
+|-
+|[https://doi.org/10.1016/S1470-2045(19)30178-0 Vergote et al. 2019 (TRINOVA-3)]
+|2012-2014
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trebananib|TC & Trebananib]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6941439/ Coleman et al. 2019 (VELIA)]
+|rowspan=2|2015-2017
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib|TC & Veliparib]] x 6
+|style="background-color:#d3d3d3"|Not reported
+|-
+|2. [[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib|TC & Veliparib]] x 6, then [[#Veliparib_monotherapy_777|Veliparib maint.]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00342-9 Monk et al. 2021 (JAVELIN Ovarian 100)]
+|2016-2018
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Avelumab_999|CP & Avelumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_then_Avelumab_999|CP, then Avelumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+''<sup>1</sup>Reported efficacy for ICON7 is based on the 2015 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycle for up to 6 to 8 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*B9E-US-S302, patients with CR: Optional [[#Paclitaxel_monotherapy|paclitaxel]] consolidation
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-Supportive medications:
+===Regimen variant #6, q3wk AUC 6/180 {{#subobject:5a09cb|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(09)61157-0 Katsumata et al. 2009 (JGOG 3016)]
+|2003-2005
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]; dose-dense
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 180 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
 *"Standard premedication"
+'''21-day cycle for 6 to 9 cycles, depending on response'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #7, AUC 6/185 {{#subobject:797f8c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Dates of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1093/jnci/djg036 du Bois et al. 2003 (AGO-OVAR 3)]
+|1995-1997
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+| style="background-color:#eeee01" |Non-inferior PFS
+| style="background-color:#1a9850" |Superior QoL
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 to 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 185 mg/m<sup>2</sup> (maximum dose of 400 mg) IV over 3 hours once on day 1, '''given first'''
+'''21-day cycle for 6 or more cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #5, Gordon et al. 2011===
+===Regimen variant #8, q3wk AUC 7/175 {{#subobject:b66b7b|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1093/annonc/mdi223 Aravantinos et al. 2005]
+|1995-1999
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29.2FCisplatin_.26_Paclitaxel_999|CP/Cisplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/j.ejca.2008.06.035 Aravantinos et al. 2008]
+|1999-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel_333|Cisplatin, Doxorubicin, Paclitaxel]]
+| style="background-color:#fee08b" |Might have inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 7 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #9, q3wk AUC 7.5/175 {{#subobject:8dddc3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2003.02.153 Ozols et al. 2003 (GOG 158)]
+|Not reported
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+|style="background-color:#eeee01"|Seems to have non-inferior RFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 7.5 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] with one of the following options:
+**20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
+**20 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+# Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. [https://doi.org/10.1200/JCO.2000.18.17.3084 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963636/ PubMed]
+# '''GOG 158:''' Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. Epub 2003 Jul 14. [https://doi.org/10.1200/jco.2003.02.153 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12860964/ PubMed]
+# '''AGO-OVAR 3:''' du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, Pfisterer J; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9. [https://doi.org/10.1093/jnci/djg036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12953086/ PubMed]
+# '''SCOTROC-1:''' Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. [https://doi.org/10.1093/jnci/djh323 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15547181/ PubMed] [https://clinicaltrials.gov/study/NCT00003998 NCT00003998]
+# Aravantinos G, Fountzilas G, Kosmidis P, Dimopoulos MA, Stathopoulos GP, Pavlidis N, Bafaloukos D, Papadimitriou C, Karpathios S, Georgoulias V, Papakostas P, Kalofonos HP, Grimani E, Skarlos DV; Hellenic Cooperative Oncology Group. Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study. Ann Oncol. 2005 Jul;16(7):1116-22. Epub 2005 May 31. [https://doi.org/10.1093/annonc/mdi223 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15928071/ PubMed]
+<!-- # '''Abstract:''' A. du Bois, M. Combe, J. Rochon, C. Jackisch, E. Malaurie, H. J. Lueck, S. Loibl, W. Schroeder, A. Burges, and B. Weber. Epirubicin/paclitaxel/carboplatin (TEC) vs paclitaxel/carboplatin (TC) in first-line treatment of ovarian cancer (OC) FIGO stages IIB–IV. An AGO-GINECO Intergroup phase III trial. Journal of Clinical Oncology 2004 22:14_suppl, 5007-5007 [https://doi.org/10.1200/jco.2004.22.90140.5007 link to abstract] -->
+# '''AGO-OVAR 5:''' du Bois A, Weber B, Rochon J, Meier W, Goupil A, Olbricht S, Barats JC, Kuhn W, Orfeuvre H, Wagner U, Richter B, Lueck HJ, Pfisterer J, Costa S, Schroeder W, Kimmig R, Pujade-Lauraine E; Arbeitsgemeinschaft Gynaekologische Onkologie; Ovarian Cancer Study Group; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. J Clin Oncol. 2006 Mar 1;24(7):1127-35. [https://doi.org/10.1200/JCO.2005.03.2938 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16505432/ PubMed]
+# '''HIDOC-EIS:''' Möbus V, Wandt H, Frickhofen N, Bengala C, Champion K, Kimmig R, Ostermann H, Hinke A, Ledermann JA; AGO-OVAR; AIO; EBMT. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol. 2007 Sep 20;25(27):4187-93. Epub 2007 Aug 13. [https://doi.org/10.1200/JCO.2006.09.7527 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17698804/ PubMed] [https://clinicaltrials.gov/study/NCT00004921 NCT00004921]
+# '''MITO-2:''' Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. [https://doi.org/10.1186/1471-2407-6-202 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16882344/ PubMed] [https://clinicaltrials.gov/study/NCT00326456 NCT00326456]
+## '''Update:''' Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. Epub 2011 Aug 15. [https://doi.org/10.1200/jco.2010.33.8566 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21844495/ PubMed]
+# '''GRACES:''' Alberts DS, Marth C, Alvarez RD, Johnson G, Bidzinski M, Kardatzke DR, Bradford WZ, Loutit J, Kirn DH, Clouser MC, Markman M; GRACES Clinical Trial Consortium. Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival. Gynecol Oncol. 2008 May;109(2):174-81. Epub 2008 Mar 7. [https://doi.org/10.1016/j.ygyno.2008.01.005 link to original article]  [https://pubmed.ncbi.nlm.nih.gov/18314182/ PubMed]
+# Lhommé C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM, Baekelandt MM, Gordon AN, Fracasso PM, Mietlowski WL, Jones GJ, Dugan MH. Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol. 2008 Jun 1;26(16):2674-82. [https://doi.org/10.1200/JCO.2007.14.9807 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18509179/ PubMed]
+# Aravantinos G, Fountzilas G, Bamias A, Grimani I, Rizos S, Kalofonos HP, Skarlos DV, Economopoulos T, Kosmidis PA, Stathopoulos GP, Briasoulis E, Pectasides D, Samantas E, Timotheadou E, Papadimitriou C, Papanikolaou A, Onyenadum A, Papakostas P, Bafaloukos D, Dimopoulos MA; Hellenic Cooperative Oncology Group. Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for first-line chemotherapy of advanced ovarian cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Eur J Cancer. 2008 Oct;44(15):2169-77. Epub 2008 Aug 6. [https://doi.org/10.1016/j.ejca.2008.06.035 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18691879/ PubMed]
+# '''ICON5:''' Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, Colombo N, Fowler JM, Argenta PA, De Geest K, Mutch DG, Burger RA, Swart AM, Trimble EL, Accario-Winslow C, Roth LM; Gynecologic Cancer Intergroup. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009 Mar 20;27(9):1419-25. Epub 2009 Feb 17. Erratum in: J Clin Oncol. 2009 May 1;27(13):2305. [https://doi.org/10.1200/JCO.2008.19.1684 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668552/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19224846/ PubMed] [https://clinicaltrials.gov/study/NCT00011986 NCT00011986]
+# '''JGOG 3016:''' Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K; Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. [https://doi.org/10.1016/S0140-6736(09)61157-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19767092/ PubMed] [https://clinicaltrials.gov/study/NCT00226915 NCT00226915]
+## '''Update:''' Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, Aoki D, Jobo T, Kodama S, Terauchi F, Sugiyama T, Ochiai K; Japanese Gynecologic Oncology Group. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol. 2013 Sep;14(10):1020-6. Epub 2013 Aug 13. [https://doi.org/10.1016/S1470-2045(13)70363-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23948349/ PubMed]
+<!-- # '''Abstract:''' J. Herrstedt, J. Huober, F. Priou, H. Müller, M. Baekelandt, C. Kurzeder, J. Pfisterer, A. Stähle, I. Ray-Coquard, and A. du Bois. A randomized, phase III study (AGO-OVAR-9, GINECO-TCG, NSGO-OC-0102): Gemcitabine-paclitaxel-carboplatin (TCG) versus paclitaxel-carboplatin (TC) as first-line treatment of ovarian cancer (OC): Survival of FIGO stage I-IIA patients. Journal of Clinical Oncology 2009 27:18S, LBA5510-LBA5510 [https://doi.org/10.1200/jco.2009.27.18s.lba5510 link to abstract] -->
+# '''AGO-OVAR 9:''' du Bois A, Herrstedt J, Hardy-Bessard AC, Müller HH, Harter P, Kristensen G, Joly F, Huober J, Avall-Lundqvist E, Weber B, Kurzeder C, Jelic S, Pujade-Lauraine E, Burges A, Pfisterer J, Gropp M, Staehle A, Wimberger P, Jackisch C, Sehouli J. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer. J Clin Oncol. 2010 Sep 20;28(27):4162-9. Epub 2010 Aug 23. [https://doi.org/10.1200/JCO.2009.27.4696 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20733132/ PubMed] [https://clinicaltrials.gov/study/NCT00052468 NCT00052468]
+# '''EORTC 55971:''' Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; [[Study_Groups#EORTC|EORTC]]-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. [https://doi.org/10.1056/NEJMoa0908806 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20818904/ PubMed] [https://clinicaltrials.gov/study/NCT00003636 NCT00003636]
+# '''EORTC 55012:''' Hoskins P, Vergote I, Cervantes A, Tu D, Stuart G, Zola P, Poveda A, Provencher D, Katsaros D, Ojeda B, Ghatage P, Grimshaw R, Casado A, Elit L, Mendiola C, Sugimoto A, D'Hondt V, Oza A, Germa JR, Roy M, Brotto L, Chen D, Eisenhauer EA. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel. J Natl Cancer Inst. 2010 Oct 20;102(20):1547-56. Epub 2010 Oct 11. [https://doi.org/10.1093/jnci/djq362 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20937992/ PubMed] [https://clinicaltrials.gov/study/NCT00028743 NCT00028743]
+# '''B9E-US-S302:''' Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. [https://doi.org/10.1016/j.ygyno.2011.08.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21978765/ PubMed] [https://clinicaltrials.gov/study/NCT00191646 NCT00191646]
+# '''GOG-0218:''' Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. [https://doi.org/10.1056/NEJMoa1104390 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22204724/ PubMed] [https://clinicaltrials.gov/study/NCT00262847 NCT00262847]
+##'''PRO analysis:''' Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. Epub 2012 Dec 4. [https://doi.org/10.1016/j.ygyno.2012.11.038 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4099057/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23219660/ PubMed]
+## '''Update:''' Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. [https://doi.org/10.1200/jco.19.01009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6879307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31216226/ PubMed]
+# '''ICON7:''' Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. [https://doi.org/10.1056/NEJMoa1103799 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22204725/ PubMed] [https://clinicaltrials.gov/study/NCT00483782 NCT00483782]
+##'''HRQoL analysis:''' Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013 Mar;14(3):236-43. Epub 2013 Jan 18. [https://doi.org/10.1016/s1470-2045(12)70567-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3596061/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23333117/ PubMed]
+## '''Update:''' Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ; ICON. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):928-36. Epub 2015 Jun 23. [https://doi.org/10.1016/S1470-2045(15)00086-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26115797/ PubMed]
+# '''EORTC 55981:''' Lindemann K, Christensen RD, Vergote I, Stuart G, Izquierdo MA, Kærn J, Havsteen H, Eisenhauer E, Ridderheim M, Lopez AB, Hirte H, Aavall-Lundquvist E, Vrdoljak E, Green J, Kristensen GB; Gynecologic Cancer Intergroup. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a Gynecologic Cancer Intergroup study of the NSGO, EORTC GCG and NCIC-CTG. Ann Oncol. 2012 Oct;23(10):2613-9. Epub 2012 Apr 26. [https://doi.org/10.1093/annonc/mds060 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22539562/ PubMed] [https://clinicaltrials.gov/study/NCT00004934 NCT00004934]
+<!-- # '''Abstract:''' Sandro Pignata, Giovanni Scambia, Rossella Lauria, Francesco Raspagliesi, Pierluigi Benedetti Panici, Gennaro Cormio, Dionyssios Katsaros, Roberto Sorio, Giovanna Cavazzini, Gabriella Ferrandina, Enrico Breda, Viviana Murgia, Cosimo Sacco, Nuria Maria Asensio Sierra, Carmela Pisano, Vanda Salutari, Beatrice E. Weber, Eric Pujade-Lauraine, Ciro Gallo, Francesco Perrone. A randomized multicenter phase III study comparing weekly versus every 3 weeks carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicenter Italian Trials in Ovarian Cancer (MITO-7)—European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10) and Gynecologic Cancer Intergroup (GCIG) trial. 2013 ASCO Annual Meeting abstract LBA5501.-->
+# '''MITO-7:''' Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S, Bologna A, Weber B, Raspagliesi F, Panici PB, Cormio G, Sorio R, Cavazzini MG, Ferrandina G, Breda E, Murgia V, Sacco C, Cinieri S, Salutari V, Ricci C, Pisano C, Greggi S, Lauria R, Lorusso D, Marchetti C, Selvaggi L, Signoriello S, Piccirillo MC, Di Maio M, Perrone F; MITO; GINECO; Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups; Gynecologic Cancer Intergroup. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2014 Apr;15(4):396-405. Epub 2014 Feb 28. [https://doi.org/10.1016/S1470-2045(14)70049-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/24582486/ PubMed] [https://clinicaltrials.gov/study/NCT00660842 NCT00660842]
+# '''CHORUS:''' Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. Epub 2015 May 19. [https://doi.org/10.1016/S0140-6736(14)62223-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26002111/ PubMed] ISRCTN74802813
+# '''AGO-OVAR 12:''' du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, Denison U, Vergote I, Del Campo JM, Ottevanger P, Heubner M, Minarik T, Sevin E, de Gregorio N, Bidziński M, Pfisterer J, Malander S, Hilpert F, Mirza MR, Scambia G, Meier W, Nicoletto MO, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2016 Jan;17(1):78-89. Epub 2015 Nov 16. [https://doi.org/10.1016/S1470-2045(15)00366-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26590673/ PubMed] [https://clinicaltrials.gov/study/NCT01015118 NCT01015118]
+## '''Update:''' Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. [https://doi.org/10.1002/ijc.32606 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31381147/ PubMed]
+# '''GOG-0262:''' Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O'Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016 Feb 25;374(8):738-48. [https://doi.org/10.1056/NEJMoa1505067 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26933849/ PubMed] [https://clinicaltrials.gov/study/NCT01167712 NCT01167712]
+# '''SCORPION:''' Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. Epub 2016 Mar 19. [https://doi.org/10.1016/j.ejca.2016.01.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26998845/ PubMed] [https://clinicaltrials.gov/study/NCT01461850 NCT01461850]
+<!-- Presented at the 50th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30-June 3, 2014. -->
+# '''JGOG3017:''' Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, Suzuki N, Mikami M, Yaegashi N, Kato K, Yoshikawa H, Yokoyama Y, Tanabe H, Nishino K, Nomura H, Kim JW, Kim BG, Pignata S, Alexandre J, Green J, Isonishi S, Terauchi F, Fujiwara K, Aoki D. Randomized phase III trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first-line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG trial. J Clin Oncol. 2016 Aug 20;34(24):2881-7. Epub 2016 Jul 11. [https://doi.org/10.1200/jco.2016.66.9010 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27400948/ PubMed] UMIN000000499
+# '''TRINOVA-3:''' Vergote I, Scambia G, O'Malley DM, Van Calster B, Park SY, Del Campo JM, Meier W, Bamias A, Colombo N, Wenham RM, Covens A, Marth C, Raza Mirza M, Kroep JR, Ma H, Pickett CA, Monk BJ; TRINOVA-3/ENGOT-ov2/GOG-3001 investigators. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):862-876. Epub 2019 May 7. [https://doi.org/10.1016/S1470-2045(19)30178-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31076365/ PubMed] [https://clinicaltrials.gov/study/NCT01493505 NCT01493505]
+# '''VELIA:''' Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. Epub 2019 Sep 28. [https://doi.org/10.1056/nejmoa1909707 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6941439/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31562800/ PubMed] [https://clinicaltrials.gov/study/NCT02470585 NCT02470585]
+# '''ICON8:''' Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Hook J, Coyle C, Blagden S, Brenton JD, Naik R, Perren T, Sundar S, Cook AD, Gopalakrishnan GS, Gabra H, Lord R, Dark G, Earl HM, Hall M, Banerjee S, Glasspool RM, Jones R, Williams S, Swart AM, Stenning S, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. Lancet. 2019 Dec 7;394(10214):2084-2095. Epub 2019 Nov 29.  [https://doi.org/10.1016/S0140-6736(19)32259-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902268/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31791688/ PubMed] [https://clinicaltrials.gov/study/NCT01654146 NCT01654146]
+##'''Update:''' Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Gallardo-Rincon D, Blagden S, Brenton J, Perren TJ, Sundar S, Lord R, Dark G, Hall M, Banerjee S, Glasspool RM, Hanna CL, Williams S, Scatchard KM, Nam H, Essapen S, Parkinson C, McAvan L, Swart AM, Popoola B, Schiavone F, Badrock J, Fananapazir F, Cook AD, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):919-930. Epub 2022 Jun 8. [https://doi.org/10.1016/s1470-2045(22)00283-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9630160/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35690073/ PubMed]
+# '''JAVELIN Ovarian 100:''' Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC, Bhoola SM, Sohn J, Yonemori K, Stewart RA, Zhang X, Perkins Smith J, Linn C, Ledermann JA. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Sep;22(9):1275-1289. Epub 2021 Aug 4. [https://doi.org/10.1016/s1470-2045(21)00342-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34363762/ PubMed] [https://clinicaltrials.gov/study/NCT02718417 NCT02718417]
+#'''iPocc:''' Nagao S, Fujiwara K, Yamamoto K, Tanabe H, Okamoto A, Takehara K, Saito M, Fujiwara H, Tan DSP, Yamaguchi S, Adachi S, Kikuchi A, Hirasawa T, Yokoi T, Nagai T, Sato T, Kamiura S, Fujishita A, Loong W-W, Chan K, Syks P, Olawaye A, Ryu S-Y, Shigeta H, Kondo E, Yokoyama Y, Matsumoto T, Hasegawa K, Enomoto T. Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial. NEJM Evid. 2023;2(5). [https://doi.org/10.1056/EVIDoa2200225 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38320049/ PubMed] jRCTs031180141
+# '''FLORA-5:''' [https://clinicaltrials.gov/study/NCT04498117 NCT04498117]
+# '''KEYLYNK-001:''' [https://clinicaltrials.gov/study/NCT03740165 NCT03740165]
+==Carboplatin & Paclitaxel (CP) & Bevacizumab {{#subobject:8d896f|Regimen=1}}==
+TC-BEV: '''<u>T</u>'''axol (Paclitaxel), '''<u>C</u>'''arboplatin, '''<u>BEV</u>'''acizumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, q3wk paclitaxel, standard-dose bevacizumab x 6 {{#subobject:12e241|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://doi.org/10.1056/NEJMoa1104390 Burger et al. 2011 (GOG-0218)]
+|rowspan=2|2005-2009
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#d9ef8b" |Might have superior PFS (primary endpoint)<br>Median PFS: 11.2 vs 10.3 mo<br>(HR 0.91, 95% CI 0.80-1.04)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 40.8 vs 41.1 mo<br>(HR 1.06, 95% CI 0.94-1.20)
+|-
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]] x 22
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ Chan et al. 2016 (GOG-0262)]
+|2010-2012
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|TC-Bev]]; dose-dense
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/jco.21.00306 Moore et al. 2021 (IMagyn050)]
+|2017-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Atezolizumab.2C_Bevacizumab_999|CP, Atezolizumab, Bevacizumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+''<sup>1</sup>Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.''<br>
+''Note: Decision to use bevacizumab in GOG-0262 was at the discretion of the patient; it was not a randomization.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] as follows:
+**Cycles 2 to 6: 15 mg/kg IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*GOG-0262 & IMagyn050: [[#Bevacizumab_monotherapy|Bevacizumab]] maintenance
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, q3wk paclitaxel, standard-dose bevacizumab x 22 {{#subobject:12gjc1|Variant=1}}===
+{| class="wikitable sortable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://doi.org/10.1056/NEJMoa1104390 Burger et al. 2011 (GOG-0218)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-41-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|rowspan=2|2005-2009
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 14.1 vs 10.3 mo<br>(HR 0.72, 95% CI 0.625-0.82)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 43.4 vs 41.1 mo<br>(HR 0.96, 95% CI 0.85-1.09)
+|-
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]] x 6
+|style="background-color:#d3d3d3"|Not reported
+|-
+|}
+''<sup>1</sup>Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6: AUC 6 IV over 30 minutes once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] as follows:
+**Cycles 2 to 22: 15 mg/kg IV once on day 1
+'''21-day cycle for 22 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, q3wk paclitaxel, low-dose bevacizumab {{#subobject:be6ac3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa1103799 Perren et al. 2011 (ICON7)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-38-1 <span style="color:white;">ESMO-MCBS (1)</span>]'''
+|-
+|} -->
+|2006-2009
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS<sup>1</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2015 update.''<br>
+''Note: Bevacizumab was not given with cycle 1 if chemotherapy starts within 4 weeks of surgery. The protocol linked from Perren et al. 2011 clarifies that the recommended carboplatin dose was AUC 6, but that it could be adjusted per standard practice''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6: AUC 5 to 6 IV over 30 to 60 minutes once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] as follows:
+**Cycles 1 to 6: 7.5 mg/kg IV once on day 1
+**Cycles 7 to 18: 15 mg/kg IV once on day 1
+'''21-day cycle for 18 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''21-day cycles x up to 6 cycles; patients with complete response could optionally proceed to receive consolidation'''
+===Regimen variant #4, weekly paclitaxel {{#subobject:be7cb3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544459/ Walker et al. 2019 (GOG-252)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#IP_Carboplatin.2C_IV_Paclitaxel_.26_Bevacizumab_999|IP Carboplatin, IV Paclitaxel & Bevacizumab]]<br>2. [[#IP_Cisplatin_.26_Paclitaxel.2C_IV_Paclitaxel_.26_Bevacizumab_999|IP Cisplatin & Paclitaxel, IV Paclitaxel & Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] as follows:
+**Cycles 2 to 6: 15 mg/kg IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[#Bevacizumab_monotherapy|Bevacizumab]] maintenance
+</div></div>
+===References===
+# '''GOG-0218:''' Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. [https://doi.org/10.1056/NEJMoa1104390 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22204724/ PubMed] [https://clinicaltrials.gov/study/NCT00262847 NCT00262847]
+##'''PRO analysis:''' Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. Epub 2012 Dec 4. [https://doi.org/10.1016/j.ygyno.2012.11.038 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4099057/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23219660/ PubMed]
+## '''Update:''' Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. [https://doi.org/10.1200/jco.19.01009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6879307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31216226/ PubMed]
+# '''ICON7:''' Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. [https://doi.org/10.1056/NEJMoa1103799 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22204725/ PubMed] [https://clinicaltrials.gov/study/NCT00483782 NCT00483782]
+##'''HRQoL analysis:''' Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013 Mar;14(3):236-43. Epub 2013 Jan 18. [https://doi.org/10.1016/s1470-2045(12)70567-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3596061/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23333117/ PubMed]
+## '''Update:''' Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ; ICON. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):928-36. Epub 2015 Jun 23. [https://doi.org/10.1016/S1470-2045(15)00086-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26115797/ PubMed]
+# '''GOG-0262:''' Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O'Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016 Feb 25;374(8):738-48. [https://doi.org/10.1056/NEJMoa1505067 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26933849/ PubMed] [https://clinicaltrials.gov/study/NCT01167712 NCT01167712]
+# '''GOG-252:''' Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. [https://doi.org/10.1200/JCO.18.01568 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544459/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31002578/ PubMed] [https://clinicaltrials.gov/study/NCT00951496 NCT00951496]
+# '''IMagyn050:''' Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J, Willmott L, Colombo N, Thomes-Pepin J, Liontos M, Gold MA, Garcia Y, Sharma SK, Darus CJ, Aghajanian C, Okamoto A, Wu X, Safin R, Wu F, Molinero L, Maiya V, Khor VK, Lin YG, Pignata S. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021 Jun 10;39(17):1842-1855. Epub 2021 Apr 23. [https://doi.org/10.1200/jco.21.00306 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189598/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33891472/ PubMed] [https://clinicaltrials.gov/study/NCT03038100 NCT03038100]
+##'''Update:''' Pignata S, Bookman M, Sehouli J, Miller A, Penson RT, Taskiran C, Anderson C, Hietanen S, Myers T, Madry R, Willmott L, Lortholary A, Thomes-Pepin J, Aghajanian C, McCourt C, Stuckey A, Wu X, Nishio S, Copeland LJ, He Y, Molinero L, Patel S, Lin YG, Khor VK, Moore KN. Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer. Gynecol Oncol. 2023 Oct;177:20-31. Epub 2023 Aug 23. [https://doi.org/10.1016/j.ygyno.2023.06.018 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986425/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37625235/ PubMed]
+#'''DUO-O:''' [https://clinicaltrials.gov/study/NCT03737643 NCT03737643]
+# '''FIRST<sub>OV</sub>:''' [https://clinicaltrials.gov/study/NCT03602859 NCT03602859]
-====Consolidation====
+==Carboplatin & Paclitaxel (CP) & Nintedanib {{#subobject:dd87be|Regimen=1}}==
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV once on day 1
+CP & Nintedanib: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, Nintedanib
+<br>TC & Nintedanib: '''<u>T</u>'''axol (Paclitaxel), '''<u>C</u>'''arboplatin, Nintedanib
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, q3wk AUC 5/175 {{#subobject:1b825c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00366-6 du Bois et al. 2015 (AGO-OVAR 12)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 17.2 vs 16.6 mo<br>(HR 0.84, 95% CI 0.72-0.98)
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Targeted therapy====
+*[[Nintedanib (Vargatef)]] 200 mg PO twice per day on days 2 to 21
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, q3wk AUC 6/175 {{#subobject:1ug15c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00366-6 du Bois et al. 2015 (AGO-OVAR 12)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|TC]]
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 17.2 vs 16.6 mo<br>(HR 0.84, 95% CI 0.72-0.98)
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Targeted therapy====
+*[[Nintedanib (Vargatef)]] 200 mg PO twice per day on days 2 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+# '''AGO-OVAR 12:''' du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, Denison U, Vergote I, Del Campo JM, Ottevanger P, Heubner M, Minarik T, Sevin E, de Gregorio N, Bidziński M, Pfisterer J, Malander S, Hilpert F, Mirza MR, Scambia G, Meier W, Nicoletto MO, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2016 Jan;17(1):78-89. Epub 2015 Nov 16. [https://doi.org/10.1016/S1470-2045(15)00366-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26590673/ PubMed] [https://clinicaltrials.gov/study/NCT01015118 NCT01015118]
+## '''Update:''' Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. [https://doi.org/10.1002/ijc.32606 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31381147/ PubMed]
+==Cisplatin & Paclitaxel {{#subobject:d05939|Regimen=1}}==
+TP: '''<u>T</u>'''axol (Paclitaxel) & '''<u>P</u>'''latinol (Cisplatin)
+<br>PT: '''<u>P</u>'''latinol (Cisplatin) & '''<u>T</u>'''axol (Paclitaxel)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 75/135 {{#subobject:69d2c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJM199601043340101 McGuire et al. 1996 (GOG 111)]
+|Not reported
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
+|[[Ovarian_cancer_-_historical#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 38 vs 24 mo<br>(RR 0.60, 95% CI 0.50-0.80)
+|-
+|[https://doi.org/10.1200/JCO.2000.18.1.106 Muggia et al. 2000 (GOG 132)]
+|1992-1994
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_monotherapy_999|Cisplatin]]<br>2. [[#Paclitaxel_monotherapy_999|Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/JCO.2001.19.4.1001 Markman et al. 2001 (GOG 114)]
+|1992-1995
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_monotherapy_2|Carboplatin]], then [[#IP_Cisplatin_.26_Paclitaxel|IP Cisplatin & IV Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|[https://doi.org/10.1200/jco.2003.02.153 Ozols et al. 2003 (GOG 158)]
+|Not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+|style="background-color:#eeee01"|Seems to have non-inferior RFS
+|-
+|[https://doi.org/10.1056/NEJMoa041125 Rose et al. 2004 (GOG 152)]
+|1994-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]; with interval debulking
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1056/NEJMoa052985 Armstrong et al. 2006 (GOG 172)]
+|1998-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#IP_Cisplatin_.26_Paclitaxel|IP Cisplatin & Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|[https://doi.org/10.1200/JCO.2006.10.3846 Spriggs et al. 2007 (GOG 162)]
+|Not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]; prolonged-infusion paclitaxel
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+''Note: Some references specify to give the cisplatin after the paclitaxel (i.e., on day 2)''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*GOG 111, 132, 152: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with suboptimal debulking
+*GOG 114, 158, 172: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with optimal debulking
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 or 2
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+====Supportive therapy====
+*(details vary depending on reference):
+*[[Dexamethasone (Decadron)]] with one of the following options:
+**20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
+**20 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+*"Hydration and [[:Category:Emesis_prevention|antiemetic agents]]" once on day 1, prior to cisplatin
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles x up to 12 cycles'''
+===Regimen variant #2, 75/175 {{#subobject:61acf0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/jnci/92.9.699 Piccart et al. 2000 (OV10)]
+|1994-04 to 1995-08
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
+|[[Ovarian_cancer_-_historical#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1200/JCO.2000.18.17.3084 Neijt et al. 2000]
+|1994-1997
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://ar.iiarjournals.org/content/27/1B/681.long Mouratidou et al. 2007]
+|1998-2002
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[Ovarian_cancer_-_historical#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/j.ejca.2014.07.015 van der Burg et al. 2014]
+|1999-2006
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]; weekly paclitaxel
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*OV10: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with optimal or suboptimal debulking
+*Neijt et al. 2000: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]] was recommended
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+'''21-day cycle for 6 or more cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #6, Burger et al. 2011 (GOG-0218) & Perren et al. 2011 (ICON7)===
+===Regimen variant #3, 75/185 {{#subobject:ca46db|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 17%"|Study
-style="background:#00CD00;
+!style="width: 15%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 17%"|Comparator
-border-width:2px;
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1093/jnci/djg036 du Bois et al. 2003 (AGO-OVAR 3)]
+|1995-1997
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]]
+| style="background-color:#eeee01" |Non-inferior PFS
+| style="background-color:#d73027" |Inferior QoL
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Primary_debulking_surgery|Primary debulking surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> (maximum dose of 165 mg) IV over 30 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 185 mg/m<sup>2</sup> (maximum dose of 400 mg) IV over 3 hours once on day 1, '''given first'''
+'''21-day cycle for 6 or more cycles'''
+</div></div>
+===References===
+# '''GOG 111:''' McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. [https://doi.org/10.1056/NEJM199601043340101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7494563/ PubMed]
+# '''GOG 132:''' Muggia FM, Braly PS, Brady MF, Sutton G, Niemann TH, Lentz SL, Alvarez RD, Kucera PR, Small JM. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2000 Jan;18(1):106-15. [https://doi.org/10.1200/JCO.2000.18.1.106 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10623700/ PubMed]
+# '''OV10:''' Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. [https://doi.org/10.1093/jnci/92.9.699 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10793106/ PubMed]
+# Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. [https://doi.org/10.1200/JCO.2000.18.17.3084 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963636/ PubMed]
+# '''GOG 114:''' Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://doi.org/10.1200/JCO.2001.19.4.1001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11181662/ PubMed]
+# '''GOG 158:''' Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. Epub 2003 Jul 14. [https://doi.org/10.1200/jco.2003.02.153 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12860964/ PubMed]
+# '''AGO-OVAR 3:''' du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, Pfisterer J; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9. [https://doi.org/10.1093/jnci/djg036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12953086/ PubMed]
+# '''GOG 152:''' Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM; Gynecologic Oncology Group. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004 Dec 9;351(24):2489-97. [https://doi.org/10.1056/NEJMoa041125 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15590951/ PubMed] [https://clinicaltrials.gov/study/NCT00002568 NCT00002568]
+# '''GOG 172:''' Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. [https://doi.org/10.1056/NEJMoa052985 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16394300/ PubMed] [https://clinicaltrials.gov/study/NCT00003322 NCT00003322]
+## '''Subgroup analysis:''' Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. [https://doi.org/10.1016/j.ygyno.2005.11.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16368440/ PubMed]
+# Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. [https://ar.iiarjournals.org/content/27/1B/681.long link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17348460/ PubMed]
+# '''GOG 162:''' Spriggs DR, Brady MF, Vaccarello L, Clarke-Pearson DL, Burger RA, Mannel R, Boggess JF, Lee RB, Hanly M. Phase III randomized trial of intravenous cisplatin plus a 24- or 96-hour infusion of paclitaxel in epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Oct 1;25(28):4466-71. [https://doi.org/10.1200/JCO.2006.10.3846 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17906207/ PubMed] [https://clinicaltrials.gov/study/NCT00002717 NCT00002717]
+# van der Burg ME, Onstenk W, Boere IA, Look M, Ottevanger PB, de Gooyer D, Kerkhofs LG, Valster FA, Ruit JB, van Reisen AG, Goey SH, van der Torren AM, ten Bokkel Huinink D, Kok TC, Verweij J, van Doorn HC. Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer. Eur J Cancer. 2014 Oct;50(15):2592-601. Epub 2014 Aug 2. [https://doi.org/10.1016/j.ejca.2014.07.015 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25096168/ PubMed]
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1
+=Intraperitoneal therapy=
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+==IP Carboplatin & Paclitaxel {{#subobject:cfo4rf|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e4wfg3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/EVIDoa2200225 Nagao et al. 2023 (iPocc)]
+|2010-05 to 2016-08
+|style="background-color:#1a9851"|Phase 2/3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|IV Carboplatin & Paclitaxel]]
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 23.5 vs 20.7 mo<br>(HR 0.83, 95% CI 0.69-0.99)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IP once on day 1
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+#'''iPocc:''' Nagao S, Fujiwara K, Yamamoto K, Tanabe H, Okamoto A, Takehara K, Saito M, Fujiwara H, Tan DSP, Yamaguchi S, Adachi S, Kikuchi A, Hirasawa T, Yokoi T, Nagai T, Sato T, Kamiura S, Fujishita A, Loong W-W, Chan K, Syks P, Olawaye A, Ryu S-Y, Shigeta H, Kondo E, Yokoyama Y, Matsumoto T, Hasegawa K, Enomoto T. Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial. NEJM Evid. 2023;2(5). [https://doi.org/10.1056/EVIDoa2200225 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38320049/ PubMed] jRCTs031180141
-'''21-day cycles x 6 cycles'''
+==IP Cisplatin & Paclitaxel {{#subobject:cf7ed4|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #7, Pignata et al. 2013 (MITO-7, weekly carboplatin & paclitaxel)===
+===Regimen variant #1, IV paclitaxel {{#subobject:e9b326|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1200/JCO.2001.19.4.1001 Markman et al. 2001 (GOG 114)]
-*[[Carboplatin (Paraplatin)]] AUC 2 IV once per week
+|1992-1995
-*[[Paclitaxel (Taxol)]] 60 mg/m2 IV once per week
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[Complex_multipart_regimens#GOG_114|See link]]
-'''18 administrations given'''
+| style="background-color:#91cf60" |[[Complex_multipart_regimens#GOG_114|See link]]
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[#Carboplatin_monotherapy_2|carboplatin]]; AUC 9 x 2
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IP once on day 2
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, IV/IP paclitaxel {{#subobject:e9c475|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa052985 Armstrong et al. 2006 (GOG 172)]
+|1998-2001
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]; IV
+|style="background-color:#91cf60"|Seems to have superior OS (co-primary endpoint)<br>Median OS: 65.6 vs 49.7 mo<br>(RR 0.75, 95% CI 0.58-0.97)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IP rapid infusion once on day 2
+**Walker et al. 2006 instructs that the patient be rolled onto 4 different positions every 15 minutes to evenly distribute cisplatin
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, then 60 mg/m<sup>2</sup> IP rapid infusion once on day 8
+====Supportive therapy====
+*(Varies per reference)
+*"Standard premedication" for paclitaxel
+*"Hydration and [[:Category:Emesis_prevention|antiemetic agents]]" prior to cisplatin
+*Intraperitoneal doses of cisplatin and paclitaxel are reconstituted in 2 liters of warm normal saline before infusion
+*Additional 1 liter [[normal saline]] to be infused immediately after intraperitoneal paclitaxel
+*Supportive medications left to investigator discretion
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+# '''GOG 114:''' Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://doi.org/10.1200/JCO.2001.19.4.1001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11181662/ PubMed]
+# '''GOG 172:''' Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. [https://doi.org/10.1056/NEJMoa052985 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16394300/ PubMed] [https://clinicaltrials.gov/study/NCT00003322 NCT00003322]
+## '''Subgroup analysis:''' Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. [https://doi.org/10.1016/j.ygyno.2005.11.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16368440/ PubMed]
+=Maintenance after first-line therapy=
+==Altretamine monotherapy {{#subobject:fb91d1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:284dfe|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1006/gyno.2001.6274 Rothenberg et al. 2001 (SWOG-9326)]
+|1993-1997
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Altretamine (Hexalen)]] 260 mg/m<sup>2</sup>/day PO on days 1 to 14, split into 4 daily doses
+'''28-day cycle for 6 cycles'''
+</div></div>
 ===References===
-# Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. Epub 2003 Jul 14. [http://jco.ascopubs.org/content/21/17/3194.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12860964 PubMed]
+# '''SWOG-9326:''' Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. [https://doi.org/10.1006/gyno.2001.6274 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11531286/ PubMed]
-# Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. [http://jnci.oxfordjournals.org/content/96/22/1682.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15547181 PubMed]
+## '''Update:''' Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. [https://doi.org/10.1111/j.1048-891x.2004.014204.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15086720/ PubMed]
-# Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO Investigators. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553473/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16882344 PubMed]
+==Bevacizumab monotherapy {{#subobject:1d2514|Regimen=1}}==
-# Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K; Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961157-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19767092 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-# Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. [http://www.sciencedirect.com/science/article/pii/S0090825811007037 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21978765 PubMed]
+===Regimen variant #1, 16 cycles {{#subobject:a87d26|Variant=1}}===
-# Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. [http://www.nejm.org/doi/full/10.1056/NEJMoa1104390 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22204724 PubMed]
+{| class="wikitable sortable" style="color:white; background-color:#404040"
-# Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. [http://www.nejm.org/doi/full/10.1056/NEJMoa1103799 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22204725 PubMed]
+|<small>'''FDA-recommended dose'''</small>
-# Sandro Pignata, Giovanni Scambia, Rossella Lauria, Francesco Raspagliesi, Pierluigi Benedetti Panici, Gennaro Cormio, Dionyssios Katsaros, Roberto Sorio, Giovanna Cavazzini, Gabriella Ferrandina, Enrico Breda, Viviana Murgia, Cosimo Sacco, Nuria Maria Asensio Sierra, Carmela Pisano, Vanda Salutari, Beatrice E. Weber, Eric Pujade-Lauraine, Ciro Gallo, Francesco Perrone. A randomized multicenter phase III study comparing weekly versus every 3 weeks carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicenter Italian Trials in Ovarian Cancer (MITO-7)—European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10) and Gynecologic Cancer Intergroup (GCIG) trial. 2013 ASCO Annual Meeting abstract LBA5501. [http://meetinglibrary.asco.org/content/112845-132 link to abstract]
+|-
+|}
-==Carboplatin, Paclitaxel, Bevacizumab==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===Regimen #1, Burger et al. 2011 (GOG-0218)===
+!style="width: 20%"|Study
-Level of Evidence:
+!style="width: 20%"|Dates of enrollment
-<span
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-style="background:#00CD00;
+!style="width: 20%"|Comparator
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-color:black;
+|-
-border-width:2px;
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544459/ Walker et al. 2019 (GOG-252)]
-border-style:solid;">Phase III</span>
+|2009-2011
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1
+| style="background-color:#d3d3d3" |
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+| style="background-color:#d3d3d3" |
+|-
-'''21-day cycle x 1 cycle, then'''
+|[https://doi.org/10.1200/JCO.22.01010 Pfisterer et al. 2023 (BOOST)]
+|2011-11-11 to 2013-08-06
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+|[[#Bevacizumab_monotherapy|Bevacizumab]] x 30 mo
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*BOOST: First-line [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|Carboplatin, Paclitaxel, Bevacizumab]] x 6
+*GOG-252: First-line [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|Carboplatin, Paclitaxel, Bevacizumab]] x 6 versus [[#IP_Carboplatin.2C_IV_Paclitaxel_.26_Bevacizumab_999|IP Carboplatin, IV Paclitaxel & Bevacizumab]] x 6 versus [[#IP_Cisplatin_.26_Paclitaxel.2C_IV_Paclitaxel_.26_Bevacizumab_999|IP Cisplatin & Paclitaxel, IV Paclitaxel & Bevacizumab]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
 *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycle for up to 16 cycles'''
-'''21-day cycles x 5 cycles, then'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, indefinite {{#subobject:dbffb6|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ Chan et al. 2016 (GOG-0262)]
+|2010-2012
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
+|-
+|}
+''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|Carboplatin, Paclitaxel, Bevacizumab]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
 *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles'''
-'''21-day cycles x up to 16 cycles'''
+</div></div>
-===Regimen #2, Perren et al. 2011 (ICON7)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV over 30 to 60 minutes once on day 1; the protocol linked from Perren et al. 2011 clarifies that the recommended dose was AUC 6, but that it could be adjusted "according to standard practice"
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
-*Bevacizumab is not given in cycle 1 if chemotherapy starts within 4 weeks of surgery.  If >4 weeks after surgery: [[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1
-'''21-day cycle x 1 cycle, then'''
-*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV over 30 to 60 minutes once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
-*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1
-'''21-day cycles x 5 cycles, then'''
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-'''21-day cycles x 12 cycles'''
 ===References===
-# Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. [http://www.nejm.org/doi/full/10.1056/NEJMoa1104390 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22204724 PubMed]
+# '''GOG-0262:''' Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O'Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016 Feb 25;374(8):738-48. [https://doi.org/10.1056/NEJMoa1505067 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081077/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26933849/ PubMed] [https://clinicaltrials.gov/study/NCT01167712 NCT01167712]
-# Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. [http://www.nejm.org/doi/full/10.1056/NEJMoa1103799 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22204725 PubMed]
+# '''GOG-252:''' Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. [https://doi.org/10.1200/JCO.18.01568 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544459/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31002578/ PubMed] [https://clinicaltrials.gov/study/NCT00951496 NCT00951496]
+#'''BOOST:''' Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Lueck HJ, Emons G, Meier W, Gropp-Meier M, Schroeder W, de Gregorio N, Hilpert F, Harter P. Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial. J Clin Oncol. 2023 Feb 1;41(4):893-902. Epub 2022 Nov 4. [https://doi.org/10.1200/JCO.22.01010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36332161/ PubMed] [https://clinicaltrials.gov/study/NCT01462890 NCT01462890]
-==Cisplatin & Paclitaxel==
-===Regimen, Ozols et al. 2003; Armstrong et al. 2006; Walker et al. 2006===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cisplatin (Platinol)]] 75 mg/m2 IV at an infusion rate of 1 mg/min once on day 1
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV continuous infusion over 24 hours once on day 1
-'''21-day cycles x 6 cycles'''
-Supportive medications (details vary depending on reference):
+==Niraparib monotherapy {{#subobject:e6fvd9|Regimen=1}}==
-*[[Dexamethasone (Decadron)]] 20 mg PO given twice, at 12 and 6 hours prior to chemotherapy OR 20 mg IV once 30 minutes prior to paclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
-*Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to paclitaxel
+===Regimen {{#subobject:fa77y6|Variant=1}}===
-*Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to paclitaxel
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*"Hydration and [[antiemesis|antiemetic agents]]" before cisplatin
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa1910962 González-Martín et al. 2019 (PRIMA<sub>OV</sub>)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-214-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2016-2018
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[Ovarian_cancer_-_null_regimens#Placebo|Placebo]]
+|style="background-color:#1a9850"|Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 13.8 vs 8.2 mo<br>(HR 0.66, 95% CI 0.56-0.79)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10346505/ Li et al. 2023 (PRIME<sub>OV</sub>)]
+|2018-06-29 to 2019-11-11
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Ovarian_cancer_-_null_regimens#Placebo|Placebo]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 24.8 vs 8.3 mo<br>(HR 0.45, 95% CI 0.34-0.60)
+|-
+|}
+''<sup>1</sup>Reported efficacy for PRIMA<sub>OV</sub> is for the overall population and is based on the 2023 update.''<br>
+''Note: there are studies named PRIMA and PRIME in other cancer types, not to be confused with these.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]; neither specific agents, combinations, nor doses are specified in the protocol.
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Niraparib (Zejula)]] by the following laboratory- and weight-based criteria:
+**Less than 77 kg OR platelet count less than 150 x 10<sup>9</sup>/L: 200 mg PO once per day on days 1 to 28
+**77 kg or more AND platelet count 150 x 10<sup>9</sup>/L or more: 300 mg PO once per day on days 1 to 28
+'''28-day cycle for up to 39 cycles (3 years)'''
+</div></div>
 ===References===
-# Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. Epub 2003 Jul 14. [http://jco.ascopubs.org/content/21/17/3194.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12860964 PubMed]
+# '''PRIMA<sub>OV</sub>:''' González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. Epub 2019 Sep 28. [https://doi.org/10.1056/NEJMoa1910962 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31562799/ PubMed] [https://clinicaltrials.gov/study/NCT02655016 NCT02655016]
-# Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. [http://www.nejm.org/doi/full/10.1056/NEJMoa052985 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16394300 PubMed]
+##'''Update:''' González-Martín A, Pothuri B, Vergote I, Graybill W, Lorusso D, McCormick CC, Freyer G, Backes F, Heitz F, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Malinowska IA, Shtessel L, Compton N, Mirza MR, Monk BJ. Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023 Aug;189:112908. Epub 2023 May 3. [https://doi.org/10.1016/j.ejca.2023.04.024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37263896/ PubMed]
-# Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2006 Jan;100(1):27-32. [http://www.sciencedirect.com/science/article/pii/S0090825805010012 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16368440 PubMed]
+##'''HRQoL analysis:''' Pothuri B, Han S, Chase DM, Heitz F, Burger RA, Gaba L, Van Le L, Guerra E, Bender D, Korach J, Cloven N, Churruca C, Follana P, DiSilvestro P, Baurain JF, Jardon K, Pisano C, Peen U, Mäenpää J, Gupta D, Bacqué E, Li Y, Compton N, Antonova J, Monk BJ, González-Martín A. Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial. Gynecol Oncol. 2024 May;184:168-177. Epub 2024 Feb 6. [https://doi.org/10.1016/j.ygyno.2024.01.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38325276/ PubMed]
+#'''PRIME<sub>OV</sub>:''' Li N, Zhu J, Yin R, Wang J, Pan L, Kong B, Zheng H, Liu J, Wu X, Wang L, Huang Y, Wang K, Zou D, Zhao H, Wang C, Lu W, Lin A, Lou G, Li G, Qu P, Yang H, Zhang Y, Cai H, Pan Y, Hao M, Liu Z, Cui H, Yang Y, Yao S, Zhen X, Hang W, Hou J, Wang J, Wu L. Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1230-1237. [https://doi.org/10.1001/jamaoncol.2023.2283 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10346505/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37440217/ PubMed] [https://clinicaltrials.gov/study/NCT03709316 NCT03709316]
-=Maintenance/consolidation therapy=
+#'''AGO-OVAR 28:''' [https://www.clinicaltrials.gov/study/NCT05009082 NCT05009082]
-==Altretamine (Hexalen)==
-===Regimen, Alberts et al. 2004===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Altretamine (Hexalen)]] 260 mg/m2 PO once per day on days 1 to 14
+==Paclitaxel monotherapy {{#subobject:6f7a6a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 135 mg/m<sup>2</sup> q4wk {{#subobject:b5e4cb|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2011.08.018 Gordon et al. 2011 (B9E-US-S302)]
+|2002-2006
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] x 6 versus [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for up to 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen variant #2, 175 mg/m<sup>2</sup> q3wk x 3 {{#subobject:5bb98c|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2004.10.001 Micha et al. 2005]
+|2002-07 to 2003-08
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[#PGC_888|Carboplatin, Gemcitabine, Paclitaxel]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+'''21-day cycle for 3 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 175 mg/m<sup>2</sup> q3wk x 12 {{#subobject:7d827f|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2004.10.001 Micha et al. 2005]
+|2002-07 to 2003-08
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[#PGC_888|Carboplatin, Gemcitabine, Paclitaxel]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+'''21-day cycle for 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 175 mg/m<sup>2</sup> q4wk x 3 {{#subobject:b29e5b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2003.07.013 Markman et al. 2003 (GOG 178)]
+|1997-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Paclitaxel_monotherapy|Paclitaxel]] x 12
+|style="background-color:#d73027"|Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''28-day cycle for 3 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 175 mg/m<sup>2</sup> q4wk x 12 {{#subobject:dff428|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2003.07.013 Markman et al. 2003 (GOG 178)]
+|1997-2001
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Paclitaxel_monotherapy|Paclitaxel]] x 3
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 28 vs 21 mo<br>(HR 0.43, 99% CI 0.20-0.93)
+.31 (99% confidence interval, 1.08 to 4.94
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''28-day cycle for 12 cycles'''
+</div></div>
 ===References===
-# Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. [http://www.ncbi.nlm.nih.gov/pubmed/15086720 PubMed]
+# '''GOG 178:''' Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; [[Study_Groups#SWOG|SWOG]]; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. [https://doi.org/10.1200/jco.2003.07.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12829663/ PubMed] [https://clinicaltrials.gov/study/NCT00003120 NCT00003120]
+## '''Update:''' Markman M, Liu PY, Moon J, Monk BJ, Copeland L, Wilczynski S, Alberts D. Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m<sup>2</sup>) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial. Gynecol Oncol. 2009 Aug;114(2):195-8. Epub 2009 May 17. [https://doi.org/10.1016/j.ygyno.2009.04.012 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744303/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19447479/ PubMed]
-==Paclitaxel (Taxol)==
+# Micha JP, Goldstein BH, Mattison JA, Bader K, Graham C, Rettenmaier MA, Brown JV, Markman M. Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer. Gynecol Oncol. 2005 Jan;96(1):132-5. [https://doi.org/10.1016/j.ygyno.2004.10.001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15589591/ PubMed]
-===Regimen #1, Markman et al. 2003 (GOG 178)===
+# '''Retrospective:''' Abaid LN, Goldstein BH, Micha JP, Rettenmaier MA, Brown JV 3rd, Markman M. Improved overall survival with 12 cycles of single-agent paclitaxel maintenance therapy following a complete response to induction chemotherapy in advanced ovarian carcinoma. Oncology. 2010;78(5-6):389-93. Epub 2010 Aug 27. [https://doi.org/10.1159/000320579 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20798562/ PubMed]
-Level of Evidence:
+# '''B9E-US-S302:''' Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. [https://doi.org/10.1016/j.ygyno.2011.08.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21978765/ PubMed] [https://clinicaltrials.gov/study/NCT00191646 NCT00191646]
-<span
+==Pazopanib monotherapy {{#subobject:84efa4|Regimen=1}}==
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#eeeeee">
-padding:3px 6px 3px 6px;
+===Regimen {{#subobject:a0ac84|Variant=1}}===
-border-color:black;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-width:2px;
+!style="width: 20%"|Study
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-*[[Paclitaxel (Taxol)]] 135 or 175 mg/m2 IV over 3 hours once on day 1
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-'''28-day cycles x 3 or 12 cycles'''
+|-
+|[https://doi.org/10.1200/jco.2014.55.7348 Du Bois et al. 2014 (AGO-OVAR 16)]
-===Regimen #2, Micha et al. 2005 & Abaid et al. 2010===
+|2009-06 to 2010-08
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV over 1 hour once on day 1
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Ovarian_cancer_-_null_regimens#Placebo|Placebo]]
-'''21-day cycles x 12 cycles'''
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 17.9 vs 12.3 mo<br>(HR 0.77, 95% CI 0.64-0.91)
+|-
-Supportive medications:
+|}
-*Diphenhydramine (Benadryl), [[Dexamethasone (Decadron)]], Cimetidine (Tagamet)
+''Patients enrolled in AGO-OVAR 16 had histologically confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, were FIGO II to IV, and no evidence of progression after initial treatment.''
+<div class="toccolours" style="background-color:#cbd5e8">
-===References===
+====Preceding treatment====
-# Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; Southwest Oncology Group; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. [http://jco.ascopubs.org/content/21/13/2460.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12829663 PubMed]
+*[[Surgery#Ovarian_cancer_surgery|Surgery]] and at least 5 cycles of first-line platinum and taxane combination chemotherapy
-# Micha JP, Goldstein BH, Mattison JA, Bader K, Graham C, Rettenmaier MA, Brown JV, Markman M. Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer. Gynecol Oncol. 2005 Jan;96(1):132-5. [http://www.sciencedirect.com/science/article/pii/S0090825804008091 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15589591 PubMed]
+</div>
-# '''Update:''' Markman M, Liu PY, Moon J, Monk BJ, Copeland L, Wilczynski S, Alberts D. Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m2) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial. Gynecol Oncol. 2009 Aug;114(2):195-8. Epub 2009 May 17. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744303 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19447479 PubMed]
+<div class="toccolours" style="background-color:#b3e2cd">
-# '''Retrospective''' Abaid LN, Goldstein BH, Micha JP, Rettenmaier MA, Brown JV 3rd, Markman M. Improved overall survival with 12 cycles of single-agent paclitaxel maintenance therapy following a complete response to induction chemotherapy in advanced ovarian carcinoma. Oncology. 2010;78(5-6):389-93. Epub 2010 Aug 27. [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=000320579&Ausgabe=254415&ProduktNr=223857 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20798562 PubMed]
+====Targeted therapy====
-==Pazopanib (Votrient)==
-===Regimen, Du Bois et al. 2013 (AGO-OVAR16)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''Patients enrolled in Du Bois et al. 2013 (AGO-OVAR16) had histologically confirmed advanced epithelial ovarian, fallopian tube, or  primary peritoneal cancer, were FIGO II to IV, and no evidence of progression after surgery and at least 5 cycles of platinum-taxane chemotherapy.''
 *[[Pazopanib (Votrient)]] 800 mg PO once per day
 '''24-month course'''
+</div></div>
 ===References===
-# Andreas Du Bois, Anne Floquet, Jae Weon Kim, Jörn Rau, Jose Maria Del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Pauline Wimberger, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Jae Hoon Kim, Philipp Harter. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). 2013 ASCO Annual Meeting abstract LBA5503. [http://meetinglibrary.asco.org/content/115898-132 link to abstract]
+<!-- # '''Abstract:''' Andreas Du Bois, Anne Floquet, Jae Weon Kim, Jörn Rau, Jose Maria Del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Pauline Wimberger, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Jae Hoon Kim, Philipp Harter. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). 2013 ASCO Annual Meeting abstract LBA5503.-->
+# '''AGO-OVAR 16:''' du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014 Oct 20;32(30):3374-82. Epub 2014 Sep 15. [https://doi.org/10.1200/jco.2014.55.7348 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25225436/ PubMed] [https://clinicaltrials.gov/study/NCT00866697 NCT00866697]
-==Placebo==
+## '''Subgroup analysis:''' Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib maintenance therapy in East Asian women with advanced epithelial ovarian cancer: results from AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. [https://doi.org/10.1097/igc.0000000000000602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26588236/ PubMed]
-===Regimen, Du Bois et al. 2013 (AGO-OVAR16)===
+## '''Update:''' Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. Epub 2019 Sep 10. [https://doi.org/10.1016/j.ygyno.2019.08.024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31519320/ PubMed]
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''No treatment. Used as a comparator arm and here for reference purposes only.''
-===References===
-# Andreas Du Bois, Anne Floquet, Jae Weon Kim, Jörn Rau, Jose Maria Del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Pauline Wimberger, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Jae Hoon Kim, Philipp Harter. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). 2013 ASCO Annual Meeting abstract LBA5503. [http://meetinglibrary.asco.org/content/115898-132 link to abstract]
-=Intraperitoneal therapy=
-==Cisplatin & Paclitaxel==
-===Regimen #1, Armstrong et al. 2006===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cisplatin (Platinol)]] 100 mg/m2 intraperitoneal rapid infusion once on day 2
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV continuous infusion over 24 hours once on day 1, then 60 mg/m2 intraperitoneal rapid infusion once on day 8
-'''21-day cycles x 6 cycles'''
-Supportive medications:
-*"Standard premedication" for paclitaxel
-*"Hydration and [[antiemesis|antiemetic agents]]" before cisplatin
-*Intraperitoneal doses of cisplatin and paclitaxel are reconstituted in 2 liters of warm normal saline before infusion
-===Regimen #2, Walker et al. 2006===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cisplatin (Platinol)]] 100 mg/m2 in 2 liters of normal saline, intraperitoneal rapid infusion once on day 2, with patient rolled onto 4 different positions every 15 minutes to evenly distribute cisplatin
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV continuous infusion over 24 hours once on day 1, then 60 mg/m2 in 1 liter saline, intraperitoneal rapid infusion once on day 8
-'''21-day cycles x 6 cycles'''
-Supportive medications:
-*Additional 1 liter normal saline to be infused immediately after intraperitoneal paclitaxel
-*Supportive medications left to investigator discretion
+==Rucaparib monotherapy {{#subobject:ug81a1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:acjwcf|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746782/ Monk et al. 2022 (ATHENA-MONO)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Ovarian_cancer_-_null_regimens#Placebo|Placebo]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 20.2 vs 9.2 mo<br>(HR 0.52, 95% CI 0.40-0.68)
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*First-line [[Regimen_classes#Platinum_doublet|platinum doublet chemotherapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rucaparib (Rubraca)]] 600 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
 ===References===
-# Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. [http://www.nejm.org/doi/full/10.1056/NEJMoa052985 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16394300 PubMed]
+# '''ATHENA-MONO:''' Monk BJ, Parkinson C, Lim MC, O'Malley DM, Oaknin A, Wilson MK, Coleman RL, Lorusso D, Bessette P, Ghamande S, Christopoulou A, Provencher D, Prendergast E, Demirkiran F, Mikheeva O, Yeku O, Chudecka-Glaz A, Schenker M, Littell RD, Safra T, Chou HH, Morgan MA, Drochýtek V, Barlin JN, Van Gorp T, Ueland F, Lindahl G, Anderson C, Collins DC, Moore K, Marme F, Westin SN, McNeish IA, Shih D, Lin KK, Goble S, Hume S, Fujiwara K, Kristeleit RS. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022 Dec 1;40(34):3952-3964. Epub 2022 Jun 6. [https://doi.org/10.1200/jco.22.01003 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35658487/ PubMed] [https://clinicaltrials.gov/study/NCT03522246 NCT03522246]
-# Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2006 Jan;100(1):27-32. [http://www.sciencedirect.com/science/article/pii/S0090825805010012 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16368440 PubMed]
-=Relapsed or recurrent disease=
-==Carboplatin (Paraplatin)==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
+=Second-line therapy for relapsed or recurrent disease, platinum-sensitive=
+==Carboplatin monotherapy {{#subobject:f19c03|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, AUC 5 {{#subobject:34cc91|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(03)13718-X Parmar et al. 2003 (ICON4)]
+|1996-2002
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_4|Carboplatin & Paclitaxel]]<br>1b. [[#Cisplatin_.26_Paclitaxel_3|Cisplatin & Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|[https://doi.org/10.1200/jco.2006.06.0913 Pfisterer et al. 2006 (AGO-OVAR 2.5)]
+|1999-2002
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|Carboplatin & Gemcitabine]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2276605/ Alberts et al. 2007 (SWOG S0200)]
+|2002-08 to 2004-12
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Pegylated_liposomal_doxorubicin_2|Carboplatin & PLD]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy for SWOG S0200 is based on the 2009 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+'''21-day cycle for 6 to 10 cycles'''
-'''21-day cycles x 6 to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 300 mg/m<sup>2</sup> {{#subobject:85cc91|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1006/gyno.2001.6151 Bolis et al. 2001 (ARGO 96)]
+|1991 to not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#Carboplatin_.26_Epirubicin|Carboplatin & Epirubicin]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for 5 cycles'''
+</div></div>
 ===References===
-# Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2803%2913718-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12826431 PubMed]
+# '''ARGO 96:''' Bolis G, Scarfone G, Giardina G, Villa A, Mangili G, Melpignano M, Presti M, Tateo S, Franchi M, Parazzini F; Associazione per la Ricerca in Ginecologia Oncologia Study Group. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol. 2001 Apr;81(1):3-9. [https://doi.org/10.1006/gyno.2001.6151 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11277642/ PubMed]
-# Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC CTG; EORTC GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. [http://jco.ascopubs.org/content/24/29/4699.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16966687 PubMed]
+# '''ICON4:''' Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [https://doi.org/10.1016/S0140-6736(03)13718-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12826431/ PubMed] [https://clinicaltrials.gov/study/NCT00002894 NCT00002894]
+<!-- Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004 and at the 10th Biennial Meeting of the International Gynecologic Cancer Society, Edinburgh, Scotland, October 3-7, 2004. -->
+# '''AGO-OVAR 2.5:''' Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; [[Study_Groups#EORTC|EORTC]] GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC-CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. [https://doi.org/10.1200/jco.2006.06.0913 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16966687/ PubMed] [https://clinicaltrials.gov/study/NCT00102414 NCT00102414]
+#'''SWOG S0200:''' Alberts DS, Liu PY, Wilczynski SP, Clouser MC, Lopez AM, Michelin DP, Lanzotti VJ, Markman M; Southwest Oncology Group. Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). Gynecol Oncol. 2008 Jan;108(1):90-4. Epub 2007 Oct 18. [https://doi.org/10.1016/j.ygyno.2007.08.075 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2276605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17949799/ PubMed] [https://clinicaltrials.gov/study/NCT00043082 NCT00043082]
+##'''Update:''' Markman M, Moon J, Wilczynski S, Lopez AM, Rowland KM Jr, Michelin DP, Lanzotti VJ, Anderson GL, Alberts DS. Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3 randomized trial. Gynecol Oncol. 2010 Mar;116(3):323-5. Epub 2009 Dec 30. [https://doi.org/10.1016/j.ygyno.2009.11.026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2836168/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20044128/ PubMed]
-==Carboplatin & Docetaxel==
+==Carboplatin & Docetaxel {{#subobject:8cd1bc|Regimen=1}}==
-===Regimen #1, Strauss et al. 2007===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen variant #1, AUC 2/35, 3 weeks out of 4 {{#subobject:bd8ef9|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-style="background:#EEEE00;
+!style="width: 33%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 33%"|Dates of enrollment
-border-color:black;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+|-
-border-style:solid;">Phase II</span>
+|[https://doi.org/10.1016/j.ygyno.2006.12.018 Kushner et al. 2007]
+|Not reported
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1, given second
+|style="background-color:#91cf61"|Phase 2
-*[[Docetaxel (Taxotere)]] 75 mg/m2 IV over 60 minutes once on day 1, given first
+|-
+|}
-'''21-day cycles x 6 cycles'''
+''Note: BSA was capped at 2 m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#b3e2cd">
-Supportive medications:
+====Chemotherapy====
-*[[Steroid conversions|Corticosteroids]] given twice, 12 hours and 30 minutes before docetaxel
+*[[Carboplatin (Paraplatin)]] AUC 2 IV over 30 minutes once per day on days 1, 8, 15, '''given second'''
-*Prophylactic [[antiemesis|antiemetics]] with 5-HT3 antagonist
+*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> (maximum dose of 70 mg) IV over 60 minutes once per day on days 1, 8, 15, '''given first'''
+====Supportive therapy====
-===Regimen #2, Kushner et al. 2007===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] AUC 2 IV over 30 minutes once per day on days 1, 8, 15, given second
-*[[Docetaxel (Taxotere)]] 35 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, given first
-*Body surface area capped at 2 m2
-'''28-day cycles x 6 cycles'''
-Supportive medications:
 *[[Dexamethasone (Decadron)]] 4 mg PO the evening before, the morning of, and evening after docetaxel
-*[[Antiemesis|5-HT3 antagonist]] before chemotherapy
+*[[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonist]] once per day on days 1, 8, 15, prior to chemotherapy
-*Phenothiazine or 5-HT3 antagonist as needed as an outpatient
+*[[:Category:Phenothiazines|Phenothiazine]] or [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonist]] as needed as an outpatient
-*Diphenhydramine (Benadryl) 50 mg IV once immediately prior to docetaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15, immediately prior to docetaxel
+'''28-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, AUC 5/75 {{#subobject:9c8b3f|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2006.09.023 Strauss et al. 2007]
+|2000-2003
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.2015.63.2596 Vergote et al. 2016 (FAR-131)]
+|2009 to not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 1.25 mg/kg<br>1b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 1.25 mg/kg<br>2a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 2.5 mg/kg<br>2b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 2.5 mg/kg
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00006-1 Shi et al. 2021 (SOC-1)]
+|2012-2019
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|}
+''Note: this is the lower bound of carboplatin dosing specified by FAR-131.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*SOC-1: [[Surgery#Secondary_cytoreduction|Secondary cytoreduction]] versus no surgical intervention
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1, '''given second'''
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*[[:Category:Steroids|Corticosteroids]] given twice on day 1; 12 hours and 30 minutes prior to docetaxel
+*Prophylactic [[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]]
+'''21-day cycle for varying durations: 6 cycles (FAR-131, Strauss et al. 2007); 6 to 9 cycles (SOC-1)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, AUC 6/75 {{#subobject:91cb64|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2015.63.2596 Vergote et al. 2016 (FAR-131)]
+|2009 to not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 1.25 mg/kg<br>1b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 1.25 mg/kg<br>2a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 2.5 mg/kg<br>2b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 2.5 mg/kg
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+''Note: this is the upper bound of carboplatin dosing specified by FAR-131.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div>
 ===References===
-# Strauss HG, Henze A, Teichmann A, Karbe I, Baumgart A, Thomssen C, Koelbl H. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007 Mar;104(3):612-6. Epub 2006 Oct 27. [http://www.sciencedirect.com/science/article/pii/S0090825806007906 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17069876 PubMed]
+# Strauss HG, Henze A, Teichmann A, Karbe I, Baumgart A, Thomssen C, Koelbl H. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007 Mar;104(3):612-6. Epub 2006 Oct 27. [https://doi.org/10.1016/j.ygyno.2006.09.023 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17069876/ PubMed]
-# Kushner DM, Connor JP, Sanchez F, Volk M, Schink JC, Bailey HH, Harris LS, Stewart SL, Fine J, Hartenbach EM; Wisconsin Oncology Network. Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial. Gynecol Oncol. 2007 May;105(2):358-64. Epub 2007 Jan 29. [http://www.sciencedirect.com/science/article/pii/S0090825806010171 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17258800 PubMed]
+# Kushner DM, Connor JP, Sanchez F, Volk M, Schink JC, Bailey HH, Harris LS, Stewart SL, Fine J, Hartenbach EM; Wisconsin Oncology Network. Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial. Gynecol Oncol. 2007 May;105(2):358-64. Epub 2007 Jan 29. [https://doi.org/10.1016/j.ygyno.2006.12.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17258800/ PubMed]
+# '''FAR-131:''' Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. [https://doi.org/10.1200/JCO.2015.63.2596 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27001568/ PubMed] [https://clinicaltrials.gov/study/NCT00849667 NCT00849667]
-==Carboplatin & Doxorubicin liposomal==
+# '''SOC-1:''' Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. [https://doi.org/10.1016/s1470-2045(21)00006-1 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33705695/ PubMed] [https://clinicaltrials.gov/study/NCT01611766 NCT01611766]
-===Regimen, Pujade-Lauraine et al. 2010 (CALYPSO)===
+==Carboplatin & Pegylated liposomal doxorubicin {{#subobject:a277bb|Regimen=1}}==
-Level of Evidence:
+CD: '''<u>C</u>'''arboplatin & '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin)
-<span
+<br>PLDC: '''<u>P</u>'''egylated '''<u>L</u>'''iposomal '''<u>D</u>'''oxorubicin & '''<u>C</u>'''arboplatin
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#eeeeee">
-padding:3px 6px 3px 6px;
+===Regimen {{#subobject:b45db0|Variant=1}}===
-border-color:black;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-width:2px;
+!style="width: 20%"|Study
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-CALYPSO: '''<u>Ca</u>'''e'''<u>ly</u>'''x in '''<u>P</u>'''latinum '''<u>S</u>'''ensitive '''<u>O</u>'''varian patients
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2009.25.7519 Pujade-Lauraine et al. 2010 (CALYPSO)]
+|2005-2007
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_4|Carboplatin & Paclitaxel]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 11.3 vs 9.4 mo<br>(HR 0.82, 95% CI 0.72-0.94)
+|-
+|[https://doi.org/10.1093/annonc/mdw418 Sehouli et al. 2016 (HECTOR)]
+|2007-2009
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[Stub#Carboplatin_.26_Topotecan|Carboplatin & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS12
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070417/ Colombo et al. 2023 (INOVATYON)]
+|2011-12 to 2017-09-18
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_.26_Trabectedin_999|PLD & Trabectedin]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Bevacizumab|Carboplatin, PLD, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab_2|CP & Bevacizumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ Liu et al. 2022 (NRG-GY004)]
+|2016-02-04 to 2017-11-13
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Olaparib_monotherapy_999|Olaparib]]<br>2. [[#Cediranib_.26_Olaparib_999|Cediranib & Olaparib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+''Note: CALYPSO stands for '''<u>Ca</u>'''e'''<u>ly</u>'''x (Pegylated liposomal doxorubicin) in '''<u>P</u>'''latinum '''<u>S</u>'''ensitive '''<u>O</u>'''varian patients''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
-*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV once on day 1
+*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
-'''28-day cycles x 6 or more cycles, depending on response and toxicity'''
+*"Antiemetics, including a [[:Category:Serotonin 5-HT3 antagonists|serotonin 5-HT3 antagonist]] and [[:Category:Steroids|corticosteroid]]"
+'''28-day cycle for varying durations: 4 or more cycles, depending on response and toxicity; 6 cycles (MITO 16); 6 or more cycles (CALYPSO, INOVATYON); indefinitely (HECTOR, NRG-GY004)'''
-Supportive medications:
+</div></div>
-*"[[antiemesis|Antiemetics]], including a serotonin antagonist and corticosteroid with 5-HT3 antagonist"
+===References===
+<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2009, Orlando, FL. -->
+# '''CALYPSO:''' Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. [https://doi.org/10.1200/jco.2009.25.7519 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20498395/ PubMed] [https://clinicaltrials.gov/study/NCT00189553 NCT00189553]
+## '''Update:''' Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. [https://doi.org/10.1038/bjc.2012.307 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22836511/ PubMed]
+# '''HECTOR:''' Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. [https://doi.org/10.1093/annonc/mdw418 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27789470/ PubMed] [https://clinicaltrials.gov/study/NCT00437307 NCT00437307]
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
+# '''NRG-GY004:''' Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. [https://doi.org/10.1200/jco.21.02011 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35290101/ PubMed] [https://clinicaltrials.gov/study/NCT02446600 NCT02446600]
+#'''INOVATYON:''' Colombo N, Fossati R, Gadducci A, Bologna A, Sehouli J, Rulli E, Maenpaa J, Berger R, Sessa C, Montes A, Ottevanger NB, Vergote I, D'Incalci M, Chekerov R, Nyvang GB, Riniker S, Herbertson R, Barretina-Ginesta MP, Deryal M, Mirza MR, Biagioli E, Iglesias M, Funari G, Romeo M, Churruca Galaz C, Tasca G, Pardo B, Tognon G, Rubio-Perez MJ, DeCensi A, De Giorgi U, Zola P, Benedetti Panici P, Aglietta M, Arcangeli V, Zamagni C, Westermann A, Heinzelmann-Schwarz V, Tsibulak I, Wimberger P, Poveda A. INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line. Br J Cancer. 2023 Apr;128(8):1503-1513. Epub 2023 Feb 9. [https://doi.org/10.1038/s41416-022-02108-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070417/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36759720/ PubMed] [https://clinicaltrials.gov/study/NCT01379989 NCT01379989]
+==Carboplatin, Pegylated liposomal doxorubicin, Bevacizumab {{#subobject:a38gbb|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:8ghdb0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30142-x Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18)]
+|2013-2015
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]]
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 13.3 vs 11.6 mo<br>(HR 0.81, 95% CI 0.68-0.96)
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Pegylated_liposomal_doxorubicin_2|Carboplatin & PLD]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|Carboplatin & Gemcitabine]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_4|CP]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.8 vs 8.8 mo<br>(HR 0.51, 95% CI 0.41-0.65)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ Kurtz et al. 2023 (ATALANTE)]
+|2016-09-28 to 2019-10-04
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29.2C_Atezolizumab.2C_Bevacizumab|GCb, Atezolizumab, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Atezolizumab.2C_Bevacizumab|CP, Atezolizumab, Bevacizumab]]<br>1c. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Atezolizumab.2C_Bevacizumab|Carboplatin, PLD, Atezolizumab, Bevacizumab]]
+| style="background-color:#fee08b" |Might have inferior PFS (co-primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6: AUC 5 IV once on day 1
+*[[Pegylated liposomal doxorubicin (Doxil)]] as follows:
+**Cycles 1 to 6: 30 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] as follows:
+**Cycles 1 to 6: 10 mg/kg IV once per day on days 1 & 15
+**Cycle 7 onwards: 15 mg/kg IV once on day 1
+'''28-day cycle for 6 cycles, then 21-day cycles'''
+</div></div>
 ===References===
-# Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. [http://jco.ascopubs.org/content/28/20/3323.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20498395 PubMed]
+# '''AGO-OVAR 2.21/ENGOT-ov 18:''' Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. [https://doi.org/10.1016/s1470-2045(20)30142-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32305099/ PubMed] [https://clinicaltrials.gov/study/NCT01837251 NCT01837251]
-# '''Update:''' Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. doi: 10.1038/bjc.2012.307. Epub 2012 Jul 26. [http://www.nature.com/bjc/journal/v107/n4/full/bjc2012307a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22836511 PubMed]
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
+#'''ATALANTE:''' Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. [https://doi.org/10.1200/jco.23.00529 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37643382/ PubMed] [https://clinicaltrials.gov/study/NCT02891824 NCT02891824]
-==Carboplatin & Gemcitabine==
-===Regimen, Pfisterer et al. 2006 & Aghajanian et al. 2012 (OCEANS)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
+==Carboplatin & Gemcitabine (GCb) {{#subobject:512563|Regimen=1}}==
+GCb: '''<u>G</u>'''emcitabine & '''<u>C</u>'''ar'''<u>b</u>'''oplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, limited duration {{#subobject:adfc3c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2006.06.0913 Pfisterer et al. 2006 (AGO-OVAR 2.5)]
+|1999-2002
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Carboplatin_monotherapy_3|Carboplatin]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 8.6 vs 5.8 mo<br>(HR 0.72, 95% CI 0.58-0.90)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646321/ Aghajanian et al. 2012 (OCEANS)]
+|2007-2010
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ Coleman et al. 2017 (NRG/GOG-0213)]
+|2007-2011
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Bevacizumab|Carboplatin, PLD, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab_2|CP & Bevacizumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 4 IV once on day 1
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''21-day cycle for varying durations: 6 cycles (MITO 16); 6 to 10 cycles (AGO-OVAR 2.5, OCEANS)'''
-'''21-day cycles x 6 to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, indefinite {{#subobject:4d43df|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/annonc/mdw418 Sehouli et al. 2016 (HECTOR)]
+|2007-2009
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[Stub#Carboplatin_.26_Topotecan|Carboplatin & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS12
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ Liu et al. 2022 (NRG-GY004)]
+|2016-02-04 to 2017-11-13
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Olaparib_monotherapy_999|Olaparib]]<br>2. [[#Cediranib_.26_Olaparib_999|Cediranib & Olaparib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 4 IV over 30 to 60 minutes once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
+'''21-day cycles'''
+</div></div>
 ===References===
-# Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC CTG; EORTC GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. [http://jco.ascopubs.org/content/24/29/4699.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16966687 PubMed]
+<!-- Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004 and at the 10th Biennial Meeting of the International Gynecologic Cancer Society, Edinburgh, Scotland, October 3-7, 2004. -->
-# Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23. [http://jco.ascopubs.org/content/30/17/2039.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22529265 PubMed]
+# '''AGO-OVAR 2.5:''' Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; [[Study_Groups#EORTC|EORTC]] GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC-CTG, and the EORTC GCG. J Clin Oncol. 2006 Oct 10;24(29):4699-707. Epub 2006 Sep 11. [https://doi.org/10.1200/jco.2006.06.0913 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16966687/ PubMed] [https://clinicaltrials.gov/study/NCT00102414 NCT00102414]
+<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, June 3-7, 2011, Chicago, IL. -->
-==Carboplatin, Gemcitabine, Bevacizumab==
+# '''OCEANS:''' Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. [https://doi.org/10.1200/jco.2012.42.0505 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646321/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22529265/ PubMed] [https://clinicaltrials.gov/study/NCT00434642 NCT00434642]
-===Regimen, Aghajanian et al. 2012 (OCEANS)===
+## '''Update:''' Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. Epub 2015 Aug 10. [https://doi.org/10.1016/j.ygyno.2015.08.004 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993045/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26271155/ PubMed]
-Level of Evidence:
+# '''HECTOR:''' Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. [https://doi.org/10.1093/annonc/mdw418 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27789470/ PubMed] [https://clinicaltrials.gov/study/NCT00437307 NCT00437307]
-<span
+# '''NRG/GOG-0213:''' Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. [https://doi.org/10.1016/S1470-2045(17)30279-6 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28438473/ PubMed] [https://clinicaltrials.gov/study/NCT00565851 NCT00565851]
-style="background:#00CD00;
+## '''Update:''' Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. [https://doi.org/10.1056/NEJMoa1902626 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6941470/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31722153/ PubMed]
-padding:3px 6px 3px 6px;
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
-border-color:black;
+# '''NRG-GY004:''' Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. [https://doi.org/10.1200/jco.21.02011 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35290101/ PubMed] [https://clinicaltrials.gov/study/NCT02446600 NCT02446600]
-border-width:2px;
+==Carboplatin & Gemcitabine (GCb) & Bevacizumab {{#subobject:d73384|Regimen=1}}==
-border-style:solid;">Phase III</span>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bc0424|Variant=1}}===
-====Initial therapy====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646321/ Aghajanian et al. 2012 (OCEANS)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-40-1 <span style="color:white; float: center">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2007-2010
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|GCb]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 12.4 vs 8.4 mo<br>(HR 0.48, 95% CI 0.39-0.61)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 33.6 vs 32.9 mo<br>(HR 0.95, 95% CI 0.77-1.18)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ Coleman et al. 2017 (NRG/GOG-0213)]
+|2007-2011
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30142-x Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18)]
+|2013-2015
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Bevacizumab|Carboplatin, Doxil, Bevaciuzmab]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Pegylated_liposomal_doxorubicin_2|Carboplatin & PLD]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|Carboplatin & Gemcitabine]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_4|CP]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.8 vs 8.8 mo<br>(HR 0.51, 95% CI 0.41-0.65)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ Kurtz et al. 2023 (ATALANTE)]
+|2016-09-28 to 2019-10-04
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29.2C_Atezolizumab.2C_Bevacizumab|GCb, Atezolizumab, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Atezolizumab.2C_Bevacizumab|CP, Atezolizumab, Bevacizumab]]<br>1c. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Atezolizumab.2C_Bevacizumab|Carboplatin, PLD, Atezolizumab, Bevacizumab]]
+| style="background-color:#fee08b" |Might have inferior PFS (co-primary endpoint)
+|-
+|}
+''<sup>1</sup>Reported efficacy for OS in OCEANS is based on the 2015 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 4 IV once on day 1
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1, given first
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1, '''given first'''
-'''21-day cycles x 6 to 10 cycles, based on response;''' after completing these cycles of carboplatin, gemcitabine, and bevacizumab, patients continue on bevacizumab maintenance until progression of disease or unacceptable toxicity
+'''21-day cycle for varying durations: 6 cycles (AGO-OVAR 2.21/ENGOT-ov 18, ATALANTE, MITO 16, NRG/GOG-0213); 6 to 10 cycles (OCEANS)'''
+</div>
-====Bevacizumab maintenance====
+<div class="toccolours" style="background-color:#cbd5e7">
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+====Subsequent treatment====
+*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+</div></div>
 ===References===
-# Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23. [http://jco.ascopubs.org/content/30/17/2039.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22529265 PubMed]
+<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, June 3-7, 2011, Chicago, IL. -->
+# '''OCEANS:''' Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. [https://doi.org/10.1200/jco.2012.42.0505 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646321/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22529265/ PubMed] [https://clinicaltrials.gov/study/NCT00434642 NCT00434642]
-==Carboplatin & Paclitaxel==
+## '''Update:''' Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. Epub 2015 Aug 10. [https://doi.org/10.1016/j.ygyno.2015.08.004 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993045/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26271155/ PubMed]
-===Regimen, Parmar et al. 2003 (ICON4/AGO-OVAR-2.2), Pujade-Lauraine et al. 2010 (CALYPSO)===
+# '''NRG/GOG-0213:''' Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. [https://doi.org/10.1016/S1470-2045(17)30279-6 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28438473/ PubMed] [https://clinicaltrials.gov/study/NCT00565851 NCT00565851]
-Level of Evidence:
+## '''Update:''' Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. [https://doi.org/10.1056/NEJMoa1902626 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6941470/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31722153/ PubMed]
-<span
+# '''AGO-OVAR 2.21/ENGOT-ov 18:''' Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. [https://doi.org/10.1016/s1470-2045(20)30142-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32305099/ PubMed] [https://clinicaltrials.gov/study/NCT01837251 NCT01837251]
-style="background:#00CD00;
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
-padding:3px 6px 3px 6px;
+#'''ATALANTE:''' Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. [https://doi.org/10.1200/jco.23.00529 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37643382/ PubMed] [https://clinicaltrials.gov/study/NCT02891824 NCT02891824]
-border-color:black;
+==Carboplatin & Paclitaxel (CP) {{#subobject:f8f27a|Regimen=1}}==
-border-width:2px;
+CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
-border-style:solid;">Phase III</span>
+<br>PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin
+<div class="toccolours" style="background-color:#eeeeee">
-CALYPSO: '''<u>Ca</u>'''e'''<u>ly</u>'''x in '''<u>P</u>'''latinum '''<u>S</u>'''ensitive '''<u>O</u>'''varian patients
+===Regimen variant #1, AUC 5/175, limited duration {{#subobject:9bef30|Variant=1}}===
-*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV once on day 1
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Paclitaxel (Taxol)]] 175 to 185 mg/m2 IV over 3 hours once on day 1
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ Coleman et al. 2017 (NRG/GOG-0213)]
+|2007-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab_2|Carboplatin, Paclitaxel, Bevacizumab]]
+|style="background-color:#fee08b"|Might have inferior OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2019.11.034 Vergote et al. 2019 (OAS 07OVA)]
+|2009-2013
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_micellar_777|Carboplatin & Paclitaxel micellar]]
+|style="background-color:#eeee01"|Non-inferior PFS
+|-
+|[https://doi.org/10.1200/JCO.2017.73.4293 Pignata et al. 2017 (MITO-8)]
+|2009-2015
+|style="background-color:#1a9851"|Phase 3 (C)
+|Investigator's choice<sup>1</sup> of:<br>1a. [[#Pegylated_liposomal_doxorubicin_monotherapy_999|PLD]]<br>1b. [[#Topotecan_monotherapy_999|Topotecan]]<br>1c. [[#Gemcitabine_monotherapy_999|Gemcitabine]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1200/JCO.2015.63.2596 Vergote et al. 2016 (FAR-131)]
+|2009 to not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 1.25 mg/kg<br>1b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 1.25 mg/kg<br>2a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 2.5 mg/kg<br>2b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 2.5 mg/kg
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(14)71135-0 Oza et al. 2014 (D0810C00041)]
+|2010-02-12 to 2010-07-30
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Olaparib|CP & Olaparib]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00006-1 Shi et al. 2021 (SOC-1)]
+|2012-2019
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Bevacizumab|Carboplatin, PLD, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab_2|CP & Bevacizumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+''<sup>1</sup>Initially PLD was the only option. After an amendment in 2012, topotecan, gemcitabine, or "any other drug approved in this setting" were allowed.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*SOC-1: [[Surgery#Secondary_cytoreduction|Secondary cytoreduction]] versus no surgical intervention
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Supportive therapy====
+*(varies depending on reference):
+*[[:Category:Steroids|Corticosteroids]] and prophylactic [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonist]]
+*Premedication (with steroids & antihistamines) prior to paclitaxel
+'''21-day cycle for varying durations: 6 cycles (D0810C00041, FAR-131, MITO 16); 6 to 8 cycles (NRG/GOG-0213); 6 to 9 cycles (SOC-1)'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*MITO-8, upon progression: Third-line non-platinum-based chemotherapy (NPBC)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, AUC 5/175, indefinite {{#subobject:f36665|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(03)13718-X Parmar et al. 2003 (ICON4)]
+|1996-2002
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|1a. [[#Carboplatin_monotherapy_3|Carboplatin]]<br>1b. [[#Cisplatin_monotherapy_888|Cisplatin]]
+|style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: 29 vs 24 mo<br>(HR 0.82, 95% CI 0.69-0.97)
+|-
+|[https://doi.org/10.1200/jco.2009.25.7519 Pujade-Lauraine et al. 2010 (CALYPSO)]
+|2005-2007
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Pegylated_liposomal_doxorubicin_2|Carboplatin & PLD]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1093/annonc/mdw418 Sehouli et al. 2016 (HECTOR)]
+|2007-2009
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[Stub#Carboplatin_.26_Topotecan|Carboplatin & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS12
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ Liu et al. 2022 (NRG-GY004)]
+|2016-02-04 to 2017-11-13
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Olaparib_monotherapy_999|Olaparib]]<br>2. [[#Cediranib_.26_Olaparib_999|Cediranib & Olaparib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
+*(varies depending on reference):
+*[[:Category:Steroids|Corticosteroids]] and prophylactic [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonist]]
+*Premedication (with steroids & antihistamines) prior to paclitaxel
 '''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-Supportive medications (varies depending on reference):
+===Regimen variant #3, AUC 6/175, limited duration {{#subobject:626b9d|Variant=1}}===
-*[[Steroid conversions|Corticosteroids]] and prophylactic [[antiemesis|antiemetics]] with 5-HT3 antagonist
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2019.11.034 Vergote et al. 2019 (OAS 07OVA)]
+|2009-2013
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_micellar_777|Carboplatin & Paclitaxel micellar]]
+|style="background-color:#eeee01"|Non-inferior PFS
+|-
+|[https://doi.org/10.1200/JCO.2015.63.2596 Vergote et al. 2016 (FAR-131)]
+|2009 to not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 1.25 mg/kg<br>1b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 1.25 mg/kg<br>2a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Farletuzumab_999|CP & Farletuzumab]]; 2.5 mg/kg<br>2b. [[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Farletuzumab_999|DCb & Farletuzumab]]; 2.5 mg/kg
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/s1470-2045(14)71135-0 Oza et al. 2014 (D0810C00041)]
+|2010-02-12 to 2010-07-30
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Olaparib|CP & Olaparib]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, AUC 6/175, indefinite {{#subobject:d9fae9|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ Liu et al. 2022 (NRG-GY004)]
+|2016-02-04 to 2017-11-13
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Olaparib_monotherapy_999|Olaparib]]<br>2. [[#Cediranib_.26_Olaparib_999|Cediranib & Olaparib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 to 60 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
+*(varies depending on reference):
+*[[:Category:Steroids|Corticosteroids]] and prophylactic [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonist]]
 *Premedication (with steroids & antihistamines) prior to paclitaxel
+'''21-day cycles'''
+</div></div>
+===References===
+# '''ICON4:''' Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [https://doi.org/10.1016/S0140-6736(03)13718-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12826431/ PubMed] [https://clinicaltrials.gov/study/NCT00002894 NCT00002894]
+<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2009, Orlando, FL. -->
+# '''CALYPSO:''' Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. [https://doi.org/10.1200/jco.2009.25.7519 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20498395/ PubMed] [https://clinicaltrials.gov/study/NCT00189553 NCT00189553]
+## '''Update:''' Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. [https://doi.org/10.1038/bjc.2012.307 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22836511/ PubMed]
+# '''D0810C00041:''' Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. [https://doi.org/10.1016/s1470-2045(14)71135-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25481791/ PubMed] [https://clinicaltrials.gov/study/NCT01081951 NCT01081951]
+# '''FAR-131:''' Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. [https://doi.org/10.1200/JCO.2015.63.2596 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27001568/ PubMed] [https://clinicaltrials.gov/study/NCT00849667 NCT00849667]
+# '''HECTOR:''' Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. [https://doi.org/10.1093/annonc/mdw418 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27789470/ PubMed] [https://clinicaltrials.gov/study/NCT00437307 NCT00437307]
+# '''NRG/GOG-0213:''' Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. [https://doi.org/10.1016/S1470-2045(17)30279-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28438473/ PubMed] [https://clinicaltrials.gov/study/NCT00565851 NCT00565851]
+# '''MITO-8:''' Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U, Lorusso D, Murgia V, Sorio R, Ferrandina G, Sacco C, Cormio G, Breda E, Cinieri S, Natale D, Mangili G, Pisano C, Cecere SC, Di Napoli M, Salutari V, Raspagliesi F, Arenare L, Bergamini A, Bryce J, Daniele G, Piccirillo MC, Gallo C, Perrone F. Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study. J Clin Oncol. 2017 Oct 10;35(29):3347-3353. Epub 2017 Aug 21. [https://doi.org/10.1200/JCO.2017.73.4293 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28825853/ PubMed] [https://clinicaltrials.gov/study/NCT00657878 NCT00657878]
+# '''OAS 07OVA:''' Vergote I, Bergfeldt K, Franquet A, Lisyanskaya AS, Bjermo H, Heldring N, Buyse M, Brize A. A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel. Gynecol Oncol. 2020 Feb;156(2):293-300. Epub 2019 Dec 9. [https://doi.org/10.1016/j.ygyno.2019.11.034 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31826802/ PubMed] [https://clinicaltrials.gov/study/NCT00989131 NCT00989131]
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
+# '''SOC-1:''' Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. [https://doi.org/10.1016/s1470-2045(21)00006-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33705695/ PubMed] [https://clinicaltrials.gov/study/NCT01611766 NCT01611766]
+# '''NRG-GY004:''' Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. [https://doi.org/10.1200/jco.21.02011 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242406/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35290101/ PubMed] [https://clinicaltrials.gov/study/NCT02446600 NCT02446600]
+==Carboplatin & Paclitaxel (CP) & Bevacizumab {{#subobject:87gnzf|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:12e762|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ Coleman et al. 2017 (NRG/GOG-0213)]
+|2007-2011
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_4|Carboplatin & Paclitaxel]]
+| style="background-color:#d9ef8b" |Might have superior OS (primary endpoint)<br>Median OS: 42.2 vs 37.3 mo<br>(HR 0.83, 95% CI 0.68-1.005)
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30637-9 Pignata et al. 2021 (MITO 16)]
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Pegylated_liposomal_doxorubicin_2|Carboplatin & PLD]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|Carboplatin & Gemcitabine]]<br>1c. [[#Carboplatin_.26_Paclitaxel_.28CP.29_4|CP]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.8 vs 8.8 mo<br>(HR 0.51, 95% CI 0.41-0.65)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ Kurtz et al. 2023 (ATALANTE)]
+|2016-09-28 to 2019-10-04
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29.2C_Atezolizumab.2C_Bevacizumab|GCb, Atezolizumab, Bevacizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Atezolizumab.2C_Bevacizumab|CP, Atezolizumab, Bevacizumab]]<br>1c. [[#Carboplatin.2C_Pegylated_liposomal_doxorubicin.2C_Atezolizumab.2C_Bevacizumab|Carboplatin, PLD, Atezolizumab, Bevacizumab]]
+| style="background-color:#fee08b" |Might have inferior PFS (co-primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6 up to 8: AUC 5 IV over 60 minutes once on day 1, '''given third'''
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6 up to 8: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV over 90 minutes once on day 1, '''given second'''
+**If tolerated, infusion time is reduced to 60 minutes with cycle 2, and 30 minutes with cycle 3 onwards
+'''21-day cycles'''
+</div></div>
 ===References===
-# Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2803%2913718-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12826431 PubMed]
+# '''NRG/GOG-0213:''' Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. [https://doi.org/10.1016/S1470-2045(17)30279-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5715461/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28438473/ PubMed] [https://clinicaltrials.gov/study/NCT00565851 NCT00565851]
-# Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. [http://jco.ascopubs.org/content/28/20/3323.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20498395 PubMed]
+# '''MITO 16:''' Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. [https://doi.org/10.1016/s1470-2045(20)30637-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539744/ PubMed] [https://clinicaltrials.gov/study/NCT01802749 NCT01802749]
-# '''Update:''' Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. doi: 10.1038/bjc.2012.307. Epub 2012 Jul 26. [http://www.nature.com/bjc/journal/v107/n4/full/bjc2012307a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22836511 PubMed]
+#'''ATALANTE:''' Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. Epub 2023 Aug 29. [https://doi.org/10.1200/jco.23.00529 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602539/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37643382/ PubMed]
-==Cisplatin & Gemcitabine==
-===Regimen, Rose et al. 2003===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Cisplatin (Platinol)]] 30 mg/m2 IV once per day on days 1 & 8, given second
-*[[Gemcitabine (Gemzar)]] 750 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
+==Carboplatin & Paclitaxel (CP) & Olaparib {{#subobject:5c058c|Regimen=1}}==
+CP & Olaparib: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, Olaparib
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:5d64f2|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s1470-2045(14)71135-0 Oza et al. 2014 (D0810C00041)]
+|2010-02-12 to 2010-07-30
+|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_4|Carboplatin & Paclitaxel]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 12.2 vs 9.6 mo<br>(HR 0.51, 95% CI 0.34-0.77)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6: AUC 4 IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Olaparib (Lynparza)]] as follows:
+**Cycles 1 to 6: 200 mg PO twice per day on days 1 to 10
+**Cycle 7 onwards: 400 mg PO twice per day on days 1 to 21
 '''21-day cycles'''
+</div></div>
-Supportive medications:
+===References===
-*[[Antiemesis|5-HT3 antagonists]]
+# '''D0810C00041:''' Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. [https://doi.org/10.1016/s1470-2045(14)71135-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25481791/ PubMed] [https://clinicaltrials.gov/study/NCT01081951 NCT01081951]
-*[[Steroid conversions|Corticosteroids]]
+==Cisplatin & Gemcitabine (GC) {{#subobject:b8b04f|Regimen=1}}==
-*Prochlorperazine
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:375811|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1006/gyno.2002.6850 Rose et al. 2003c]
+|Not reported
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second'''
+*[[Gemcitabine (Gemzar)]] 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given first'''
+====Supportive therapy====
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]]
+*[[:Category:Steroids|Corticosteroids]]
+*[[Prochlorperazine (Compazine)]]
 *Magnesium supplementation with cisplatin
+'''21-day cycles'''
+</div></div>
+===References===
+# Rose PG, Mossbruger K, Fusco N, Smrekar M, Eaton S, Rodriguez M. Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma. Gynecol Oncol. 2003 Jan;88(1):17-21. [https://doi.org/10.1006/gyno.2002.6850 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12504621/ PubMed]
+==Cisplatin & Paclitaxel {{#subobject:610ae9|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:8149f0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(03)13718-X Parmar et al. 2003 (ICON4)]
+|1996-2002
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|1a. [[#Carboplatin_monotherapy_3|Carboplatin]]<br>1b. [[#Cisplatin_monotherapy_888|Cisplatin]]
+|style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: 29 vs 24 mo<br>(HR 0.82, 95% CI 0.69-0.97)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+# '''ICON4:''' Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [https://doi.org/10.1016/S0140-6736(03)13718-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12826431/ PubMed] [https://clinicaltrials.gov/study/NCT00002894 NCT00002894]
+==Etoposide monotherapy {{#subobject:a7d95b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:98f6b8|Variant=1}}===
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|Dates of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.1998.16.2.405 Rose et al. 1998]
+|1992-1995
+|style="background-color:#91cf61"|Phase 2
+|ORR: 34%
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Etoposide (Vepesid)]] by the following exposure-based criteria:
+**No prior pelvic radiation: 50 mg/m<sup>2</sup> PO once per day on days 1 to 21
+**Previous pelvic radiation: 30 mg/m<sup>2</sup> PO once per day on days 1 to 21
+'''28-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*In patients with previous pelvic radiation, etoposide dose could be increased up to 50 mg/m<sup>2</sup> depending on toxicity
+</div></div>
+===References===
+# Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. [https://doi.org/10.1200/jco.1998.16.2.405 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9469322/ PubMed]
+==nab-Paclitaxel monotherapy {{#subobject:3eae7f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:f597f1|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/jco.2008.18.9548 Teneriello et al. 2009]
+|2005-2006
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+'''21-day cycle for 6 to 8 cycles'''
+</div></div>
+===References===
+# Teneriello MG, Tseng PC, Crozier M, Encarnacion C, Hancock K, Messing MJ, Boehm KA, Williams A, Asmar L. Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009 Mar 20;27(9):1426-31. Epub 2009 Feb 17. [https://doi.org/10.1200/jco.2008.18.9548 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19224848/ PubMed]
+#'''ROSELLA:''' [https://clinicaltrials.gov/study/NCT05257408 NCT05257408]
+=Relapsed or recurrent disease, platinum-resistant=
+==Altretamine monotherapy {{#subobject:gcc1d1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:28uu8e|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1006/gyno.1998.5016 Markman et al. 1998]
+|Not reported
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+''Note: there is not enough information in the FDA label to determine for sure whether this is one of the registration trials; it is representative of many phase 2 trials of this agent.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Altretamine (Hexalen)]] 260 mg/m<sup>2</sup> PO once per day on days 1 to 14
+'''28-day cycles'''
+</div></div>
 ===References===
-# Rose PG, Mossbruger K, Fusco N, Smrekar M, Eaton S, Rodriguez M. Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma. Gynecol Oncol. 2003 Jan;88(1):17-21. [http://www.sciencedirect.com/science/article/pii/S0090825802968502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12504621 PubMed]
+# Markman M, Blessing JA, Moore D, Ball H, Lentz SS; Gynecologic Oncology Group. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 1998 Jun;69(3):226-9. [https://doi.org/10.1006/gyno.1998.5016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9648592/ PubMed]
-==Cisplatin & Paclitaxel==
-===Regimen, Parmar et al. 2003 (ICON4/AGO-OVAR-2.2)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+==Bevacizumab monotherapy {{#subobject:c0034f|Regimen=1}}==
+{| class="wikitable" style="color:white; background-color:#9e4244"
+|<small>'''AIM pathway regimen 2022-08-01'''</small>
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:01c4a8|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/JCO.2007.11.5345 Burger et al. 2007]
+|2002-2004
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1200/JCO.2007.12.0782 Cannistra et al. 2007]
+|2005
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2803%2913718-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12826431 PubMed]
+# Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI; Gynecologic Oncology Group. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Nov 20;25(33):5165-71. Erratum in: J Clin Oncol. 2014 Nov 10;32(32):3686. [https://doi.org/10.1200/JCO.2007.11.5345 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18024863/ PubMed]
+# Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007 Nov 20;25(33):5180-6. Erratum in: J Clin Oncol. 2008 Apr 1;26(10):1773. [https://doi.org/10.1200/JCO.2007.12.0782 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18024865/ PubMed]
-==Docetaxel (Taxotere)==
+==Docetaxel monotherapy {{#subobject:dc6ade|Regimen=1}}==
-===Regimen, Rose et al. 2003===
+{| class="wikitable" style="color:white; background-color:#9e4244"
-Level of Evidence:
+|<small>'''AIM pathway regimen 2022-08-01'''</small>
-<span
+|-
-style="background:#EEEE00;
+|}
-padding:3px 6px 3px 6px;
+<div class="toccolours" style="background-color:#eeeeee">
-border-color:black;
+===Regimen {{#subobject:e6d351|Variant=1}}===
-border-width:2px;
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-border-style:solid;">Phase II</span>
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
-*[[Docetaxel (Taxotere)]] 100 mg/m2 IV over 1 hour once on day 1
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/s0090-8258(02)00091-4 Rose et al. 2003a]
+|1998-06 to 2000-01
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1, immediately prior to docetaxel
+*[[:Category:Emesis prevention|Antiemetics]] as needed
 '''21-day cycles'''
+</div></div>
-Supportive medications:
-*[[Dexamethasone (Decadron)]] 8 mg PO BID starting 24 hours before docetaxel, and continuing for 48 hours after docetaxel
-*Diphenhydramine (Benadryl) 50 mg IV immediately prior to paclitaxel
-*[[Antiemesis|Antiemetics]] as needed
 ===References===
-# Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Feb;88(2):130-5. [http://www.sciencedirect.com/science/article/pii/S0090825802000914 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12586591 PubMed]
+# Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH; Gynecologic Oncology Group. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Feb;88(2):130-5. [https://doi.org/10.1016/s0090-8258(02)00091-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12586591/ PubMed]
+==Etoposide monotherapy {{#subobject:a7d95b|Regimen=1}}==
-==Doxorubicin liposomal (Doxil)==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #1, Gordon et al. 2004 & Mutch et al. 2007===
+===Regimen {{#subobject:98f6b8|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
-<span
+!style="width: 25%"|Study
-style="background:#00CD00;
+!style="width: 25%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-border-width:2px;
+|-
-border-style:solid;">Phase III</span>
+|[https://doi.org/10.1200/jco.1998.16.2.405 Rose et al. 1998]
+|1992-1995
-*[[Doxorubicin liposomal (Doxil)]] 50 mg/m2 IV over 60 minutes once on day 1
+|style="background-color:#91cf61"|Phase 2
+|ORR: 27%
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Etoposide (Vepesid)]] by the following exposure-based criteria:
+**No prior pelvic radiation: 50 mg/m<sup>2</sup> PO once per day on days 1 to 21
+**Previous pelvic radiation: 30 mg/m<sup>2</sup> PO once per day on days 1 to 21
 '''28-day cycles'''
+</div>
-===Regimen #2, Ferrandina et al. 2008; Pujade-Lauraine et al. 2014 (AURELIA); Stockler et al. 2014 (AURELIA)===
+<div class="toccolours" style="background-color:#fff2ae">
-Level of Evidence:
+====Dose and schedule modifications====
-<span
+*In patients with previous pelvic radiation, etoposide dose could be increased up to 50 mg/m<sup>2</sup> depending on toxicity
-style="background:#00CD00;
+</div></div>
-padding:3px 6px 3px 6px;
+===References===
-border-color:black;
+# Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. [https://doi.org/10.1200/jco.1998.16.2.405 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9469322/ PubMed]
-border-width:2px;
+==Gemcitabine monotherapy {{#subobject:4d5e38|Regimen=1}}==
-border-style:solid;">Phase III</span>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 2 weeks out of 3 {{#subobject:562314|Variant=1}}===
-*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV over 60 minutes once on day 1
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2006.09.6735 Mutch et al. 2007 (B9E-US-S301)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/jco.2015.66.0787 Kurzeder et al. 2016 (PENELOPE)]
+|2013-10-02 to 2014-09-18
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Gemcitabine_.26_Pertuzumab_999|Gemcitabine & Pertuzumab]]<br>1b. [[#Paclitaxel_.26_Pertuzumab_999|Paclitaxel & Pertuzumab]]<br>1c. [[#Topotecan_.26_Pertuzumab_999|Topotecan & Pertuzumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 8
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 3 weeks out of 4 {{#subobject:30324a|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2007.13.6606 Ferrandina et al. 2008 (MITO-3)]
+|2003-2007
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
+|style="background-color:#d9ef8b"|Might have superior ORR (secondary endpoint)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10792546/ Lheureux et al. 2021 (PHL-093)]
+|2014-2018
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Adavosertib_.26_Gemcitabine_777|Adavosertib & Gemcitabine]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601279/ Hamanishi et al. 2021 (NINJA)]
+|2015-10-07 to 2017-12-21
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Nivolumab_monotherapy_999|Nivolumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<br>Median OS: 12.1 vs 10.1 mo<br>(HR 1.00, 95% CI 0.77-1.25)
+|-
+|[https://www.clinicaltrials.gov/study/NCT04679064 Awaiting publication (NItCHE)]
+|2020-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Niraparib_.26_Dostarlimab_666|Niraparib & Dostarlimab]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 '''28-day cycles'''
+</div></div>
-Supportive medications:
-*[[Methylprednisolone (Solumedrol)]] 20 mg IV once 30 minutes prior to chemotherapy
 ===References===
-# Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. [http://www.sciencedirect.com/science/article/pii/S0090825804005232 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15385103 PubMed]
+<!-- Presented in part at the 29th European Congress on Clinical Oncology, October 30-November 3, 2005, Paris, France; and at the 37th Annual Meeting of the Society of Gynecologic Oncologists, March 22-26, 2006, Palm Springs, CA. -->
-# Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. [http://jco.ascopubs.org/content/25/19/2811.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17602086 PubMed] content property of [http://hemonc.org HemOnc.org]
+# '''B9E-US-S301:''' Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. [https://doi.org/10.1200/jco.2006.09.6735 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17602086/ PubMed] [https://clinicaltrials.gov/study/NCT00191607 NCT00191607]
-# Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. [http://jco.ascopubs.org/content/26/6/890.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18281662 PubMed]
+# '''MITO-3:''' Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. [https://doi.org/10.1200/jco.2007.13.6606 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18281662/ PubMed]
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+# '''PENELOPE:''' Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. [https://doi.org/10.1200/jco.2015.66.0787 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27269942/ PubMed] [https://clinicaltrials.gov/study/NCT01684878 NCT01684878]
+## '''Update:''' Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. [https://doi.org/10.1136/ijgc-2019-000370 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31420414/ PubMed]
-==Doxorubicin liposomal & Bevacizumab==
+#'''PHL-093:''' Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. [https://doi.org/10.1016/s0140-6736(20)32554-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10792546/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33485453/ PubMed] [https://clinicaltrials.gov/study/NCT02101775 NCT02101775]
-===Regimen, Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA)===
+#'''NINJA:''' Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. [https://doi.org/10.1200/jco.21.00334 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601279/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34473544/ PubMed] JapicCTI-153004
-Level of Evidence:
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV once on day 1
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+==Gemcitabine & Pegylated liposomal doxorubicin {{#subobject:ea7f9f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7e0b4a|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2005.04.018 Ferrandina et al. 2005]
+|2000-12 to 2004-01
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
+*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*[[Metoclopramide (Reglan)]] once per day on days 1 & 8, prior to chemotherapy
+'''21-day cycles'''
+</div></div>
 ===References===
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+# Ferrandina G, Paris I, Ludovisi M, D'Agostino G, Testa A, Lorusso D, Zanghi M, Pisconti S, Pezzella G, Adamo V, Breda E, Scambia G. Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol. 2005 Aug;98(2):267-73. [https://doi.org/10.1016/j.ygyno.2005.04.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15975643/ PubMed]
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+==Mirvetuximab soravtansine monotherapy {{#subobject:59gjzv|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Doxorubicin liposomal & Gemcitabine==
+===Regimen {{#subobject:1ugjzgu|Variant=1}}===
-===Regimen, Ferrandina et al. 2005===
+{| class="wikitable" style="color:white; background-color:#404040"
-Level of Evidence:
+|<small>'''FDA-recommended dose'''</small>
-<span
+|-
-style="background:#EEEE00;
+|}
-padding:3px 6px 3px 6px;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-color:black;
+!style="width: 20%"|Study
-border-width:2px;
+!style="width: 20%"|Dates of enrollment
-border-style:solid;">Phase II</span>
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
-*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV over 60 minutes once on day 1, given first
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
+|-
+|[https://doi.org/10.1016/j.annonc.2021.02.017 Moore et al. 2021 (FORWARD I)]
+|2017-01-24 to 2018-04-23
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
+|Physician's choice of:<br>1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|Pegylated liposomal doxorubicin]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 4.1 vs 4.4 mo<br>(HR 0.98, 95% CI 0.73-1.31)
+|-
+|[https://doi.org/10.1056/nejmoa2309169 Moore et al. 2023 (MIRASOL)]
+|2020-02-03 to NR
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|Physician's choice of:<br>1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|Pegylated liposomal doxorubicin]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+| style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: 16.46 vs 12.75 mo<br>(HR 0.67, 95% CI 0.50-0.89)<br><br>Superior PFS (primary endpoint)<br>RMPFS12: 6.13 vs 4.72 mo
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10150846/ Matulonis et al. 2023 (SORAYA)]
+|2020-06 to 2021-05
+| style="background-color:#91cf61" |Non-randomized (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|}
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Antibody-drug conjugate therapy====
+*[[Mirvetuximab soravtansine (Elahere)]] 6 mg/kg (based on adjusted ideal body weight) IV once on day 1
 '''21-day cycles'''
+</div></div>
-Supportive medications:
-*Metoclopramide (Reglan) before chemotherapy
 ===References===
-# Ferrandina G, Paris I, Ludovisi M, D'Agostino G, Testa A, Lorusso D, Zanghi M, Pisconti S, Pezzella G, Adamo V, Breda E, Scambia G. Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol. 2005 Aug;98(2):267-73. [http://www.sciencedirect.com/science/article/pii/S0090825805003173 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15975643 PubMed]
+# '''FORWARD I:''' Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. [https://doi.org/10.1016/j.annonc.2021.02.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33667670/ PubMed] [https://clinicaltrials.gov/study/NCT02631876 NCT02631876]
+# '''SORAYA:''' Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. Epub 2023 Jan 30. [https://doi.org/10.1200/jco.22.01900 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10150846/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36716407/ PubMed] [https://clinicaltrials.gov/study/NCT04296890 NCT04296890]
-==Etoposide (Vepesid)==
+#'''MIRASOL:''' Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. [https://doi.org/10.1056/nejmoa2309169 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38055253/ PubMed] [https://clinicaltrials.gov/study/NCT04209855 NCT04209855]
-===Regimen, Rose et al. 1998===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Etoposide (Vepesid)]] 50 mg/m2 PO once per day on days 1 to 21
-**Dosage for patients with previous pelvic radiation was Etoposide (Vepesid) 30 mg/m2 PO once per day on days 1 to 21; dose could be increased up to 50 mg/m2 depending on toxicity
+==Paclitaxel monotherapy {{#subobject:57d35e|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 80 mg/m<sup>2</sup> 3 out of 4 weeks {{#subobject:3fdjgu|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(15)70115-4 Pignata et al. 2015 (MITO 11)]
+|2010-2013
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Paclitaxel_.26_Pazopanib|Paclitaxel & Pazopanib]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/j.annonc.2021.02.017 Moore et al. 2021 (FORWARD I)]
+|2017-01-24 to 2018-04-23
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04679064 Awaiting publication (NItCHE)]
+|2020-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Niraparib_.26_Dostarlimab_666|Niraparib & Dostarlimab]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*FORWARD I: High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 '''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 80 mg/m<sup>2</sup> weekly {{#subobject:3fd910|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2005.10.036 Markman et al. 2006]
+|Not reported
+|style="background-color:#91cf61"|Phase 2
+|style="background-color:#d3d3d3"|
+|style="background-color:#d3d3d3"|
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5318972/ Lindemann et al. 2017 (Ovaresist)]
+|2002-2007
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Tamoxifen_monotherapy_999|Tamoxifen]]
+|style="background-color:#1a9850"|Superior PFS<sup>1</sup>
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]<br>1b. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>1c. [[#Topotecan_.26_Bevacizumab|Topotecan & Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/S1470-2045(14)70244-X Monk et al. 2014 (TRINOVA-1)]
+|2010-2012
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Paclitaxel_.26_Trebananib_777|Paclitaxel & Trebananib]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1200/jco.2015.66.0787 Kurzeder et al. 2016 (PENELOPE)]
+|2013-10-02 to 2014-09-18
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Gemcitabine_.26_Pertuzumab_999|Gemcitabine & Pertuzumab]]<br>1b. [[#Paclitaxel_.26_Pertuzumab_999|Paclitaxel & Pertuzumab]]<br>1c. [[#Topotecan_.26_Pertuzumab_999|Topotecan & Pertuzumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/jco.22.02915 Arend et al. 2023 (OVAL)]
+|2017-12 to 2022-03
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Ofranergene_obadenovec_monotherapy_999|Ofra-vec]]
+|style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS
+|-
+|[https://doi.org/10.1056/nejmoa2309169 Moore et al. 2023 (MIRASOL)]
+|2020-02-03 to NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''<sup>1</sup>Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.''<br>
+''Note: PENELOPE reported giving paclitaxel on days 1, 8, 15 of a 21-day cycle, which is identical to the schedule below.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*MIRASOL: High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 10 mg IV or PO once on day 1; 30 to 60 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 25 to 50 mg IV once on day 1; 30 to 60 minutes prior to paclitaxel
+*[[:Category:H2-receptor_antagonists|H2 blocker]] once on day 1; 30 to 60 minutes prior to paclitaxel
+'''7-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 175 mg/m<sup>2</sup>, q3wk, 3-hour infusion {{#subobject:3fd910|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1994.12.12.2654 Eisenhauer et al. 1994]
+|1991-07-23 to 1992-03-06
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Paclitaxel_monotherapy_2|Paclitaxel]]; 135 mg/m<sup>2</sup>
+|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR<br><br>Seems to have superior PFS (secondary endpoint)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034015/ Gore et al. 1995]
+|1992-1993
+| style="background-color:#91cf61" |Non-randomized
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.1997.15.6.2183 ten Bokkel Huinink et al. 1997]
+|Not reported
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Topotecan_monotherapy|Topotecan]]
+| style="background-color:#fee08b" |Might have inferior TTP<sup>1</sup>
+|-
+|[https://doi.org/10.1200/JCO.2002.20.5.1232 Cantù et al. 1999]
+|1992-1995
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|[[Ovarian_cancer_-_historical#CISCA_2|CAP]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409494/ Buda et al. 2004]
+|1994-1999
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Epirubicin_.26_Paclitaxel_.28EP.29_999|Epirubicin & Paclitaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://clinicaltrials.gov/study/NCT00653952 Awaiting publication (DOXIL-CAN-301)]
+|1997-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
+|style="background-color:#d3d3d3"|Not available<sup>2</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.''<br>
+''<sup>2</sup>DOXIL-CAN-301 appears to have been published in abstract form only, in 2002; this abstract is no longer available.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #4, 175 mg/m<sup>2</sup>, q3wk, 24-hour infusion {{#subobject:3fd240|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#f01e2c"
+|<small><span style="color:white;">'''Historic variant'''</span></small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2003.10.082 Omura et al. 2003]
+|1992-1995
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Paclitaxel_monotherapy_2|Paclitaxel]]; 250 mg/m<sup>2</sup>
+| style="background-color:#fc8d59" |Seems to have inferior ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 200 mg/m<sup>2</sup>, q3wk {{#subobject:3fd703|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1080/028418602320404998 Rosenberg et al. 2002]
+|1995-1998
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Paclitaxel_monotherapy_2|Paclitaxel]]; weekly 67 mg/m<sup>2</sup>
+|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #6, with range {{#subobject:3fd210|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#f01e2c"
+|<small><span style="color:white;">'''Historic variant'''</span></small>
+|-
+|}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.7326/0003-4819-111-4-273 McGuire et al. 1989]
+|Not reported
+| style="background-color:#91cf61" |Phase 2
+|-
+|[https://doi.org/10.1093/jnci/86.1.18 Kohn et al. 1994]
+|1991-01-01 to 1992-04-01
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]]
+</div></div>
 ===References===
-# Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. [http://jco.ascopubs.org/content/16/2/405.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9469322 PubMed]
+# McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989 Aug 15;111(4):273-9. [https://doi.org/10.7326/0003-4819-111-4-273 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2569287/ PubMed]
+# Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N, Bacon M, Santabarbara P, Onetto N, Winograd B, Canetta R. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994 Dec;12(12):2654-66. [https://doi.org/10.1200/JCO.1994.12.12.2654 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7989941/ PubMed]
-==Gemcitabine (Gemzar)==
+# Kohn EC, Sarosy G, Bicher A, Link C, Christian M, Steinberg SM, Rothenberg M, Adamo DO, Davis P, Ognibene FP, Cunnion RE, Reed E. Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst. 1994 Jan 5;86(1):18-24. [https://doi.org/10.1093/jnci/86.1.18 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7505830/ PubMed]
-===Regimen #1, Mutch et al. 2007===
+# Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H, Thompson JM. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer. 1995 Oct;72(4):1016-9. [https://doi.org/10.1038/bjc.1995.453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034015/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/7547214/ PubMed]
-Level of Evidence:
+# ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. [https://doi.org/10.1200/JCO.1997.15.6.2183 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9196130/ PubMed]
-<span
+## '''Update:''' ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. [https://doi.org/10.1093/annonc/mdh025 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14679127/ PubMed]
-style="background:#00CD00;
+# Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. [https://doi.org/10.1200/JCO.2002.20.5.1232 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11870165/ PubMed]
-padding:3px 6px 3px 6px;
+# Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, Parö G. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta Oncol. 2002;41(5):418-24. [https://doi.org/10.1080/028418602320404998 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12442916/ PubMed]
-border-color:black;
+# Omura GA, Brady MF, Look KY, Averette HE, Delmore JE, Long HJ, Wadler S, Spiegel G, Arbuck SG. Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: an intergroup study. J Clin Oncol. 2003 Aug 1;21(15):2843-8. Epub 2003 Jun 13. [https://doi.org/10.1200/JCO.2003.10.082 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12807937/ PubMed]
-border-width:2px;
+# Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C; GONO. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, GONO (Gruppo Oncologico Nord Ovest) group and IOR (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004 Jun 1;90(11):2112-7. [https://doi.org/10.1038/sj.bjc.6601787 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409494/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15150623/ PubMed]
-border-style:solid;">Phase III</span>
+# Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S; Gynecologic Oncology Group. Phase II trial of weekly paclitaxel (80 mg/m<sup>2</sup>) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jun;101(3):436-40. Epub 2005 Dec 2. [https://doi.org/10.1016/j.ygyno.2005.10.036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16325893/ PubMed]
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
-'''21-day cycles'''
+# '''TRINOVA-1:''' Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 Jul;15(8):799-808. Epub 2014 Jun 17. [https://doi.org/10.1016/S1470-2045(14)70244-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/24950985/ PubMed] [https://clinicaltrials.gov/study/NCT01204749 NCT01204749]
+## '''Update:''' Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Ma H, Vogl FD, Bach BA, Oza AM. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol. 2016 Oct;143(1):27-34. Epub 2016 Aug 18. [https://doi.org/10.1016/j.ygyno.2016.07.112 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27546885/ PubMed]
-===Regimen #2, Ferrandina et al. 2008===
+# '''MITO 11:''' Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. [https://doi.org/10.1016/S1470-2045(15)70115-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25882986/ PubMed] [https://clinicaltrials.gov/study/NCT01644825 NCT01644825]
-Level of Evidence:
+<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
-<span
+# '''PENELOPE:''' Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. [https://doi.org/10.1200/jco.2015.66.0787 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27269942/ PubMed] [https://clinicaltrials.gov/study/NCT01684878 NCT01684878]
-style="background:#00CD00;
+## '''Update:''' Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. [https://doi.org/10.1136/ijgc-2019-000370 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31420414/ PubMed]
-padding:3px 6px 3px 6px;
+# '''Ovaresist:''' Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. [https://doi.org/10.1038/bjc.2016.435 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5318972/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28118323/ PubMed] [https://clinicaltrials.gov/study/NCT02728622 NCT02728622]
-border-color:black;
+# '''FORWARD I:''' Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. [https://doi.org/10.1016/j.annonc.2021.02.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33667670/ PubMed] [https://clinicaltrials.gov/study/NCT02631876 NCT02631876]
-border-width:2px;
+# '''OVAL:''' Arend RC, Monk BJ, Shapira-Frommer R, Haggerty AF, Alvarez EA, Amit A, Alvarez Secord A, Muller C, Casado Herraez A, Herzog TJ, Tewari KS, Cohen JG, Huang M, Yachnin A, Holeman LL, Ledermann JA, Rachmilewitz Minei T, Buyse M, Fain Shmueli S, Lavi M, Harats D, Penson RT; OVAL/GOG-3018 Investigators. Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018). J Clin Oncol. 2024 Jan 10;42(2):170-179. Epub 2023 Oct 31. [https://doi.org/10.1200/jco.22.02915 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37906726/ PubMed] [https://clinicaltrials.gov/study/NCT03398655 NCT03398655]
-border-style:solid;">Phase III</span>
+#'''MIRASOL:''' Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. [https://doi.org/10.1056/nejmoa2309169 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38055253/ PubMed] [https://clinicaltrials.gov/study/NCT04209855 NCT04209855]
+# '''AGO-OVAR 2.29:''' [https://clinicaltrials.gov/study/NCT03353831 NCT03353831]
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
+# '''DOXIL-CAN-301:''' [https://clinicaltrials.gov/study/NCT00653952 NCT00653952]
+# '''EPIK-O:''' [https://clinicaltrials.gov/study/NCT04729387 NCT04729387]
+# '''GOG-3059:''' [https://clinicaltrials.gov/study/NCT04729608 NCT04729608]
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
+==Paclitaxel & Bevacizumab {{#subobject:cb482a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:38effd|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-37-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 6.7 vs 3.4 mo<br>(HR 0.48, 95% CI 0.38-0.60)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 '''28-day cycles'''
+</div></div>
 ===References===
-# Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. [http://jco.ascopubs.org/content/25/19/2811.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17602086 PubMed]
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
-# Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. [http://jco.ascopubs.org/content/26/6/890.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18281662 PubMed]
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
-==Olaparib (Lynparza)==
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
-===Regimen, Audeh et al. 2010 & Gelmon et al. 2011===
+==Paclitaxel & Pazopanib {{#subobject:e5d0ca|Regimen=1}}==
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen {{#subobject:af50ec|Variant=1}}===
-style="background:#EEEE00;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Study
-border-color:black;
+!style="width: 20%"|Dates of enrollment
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase II</span>
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Olaparib (Lynparza)]] 400 mg PO BID on days 1 to 28
+|-
+|[https://doi.org/10.1016/S1470-2045(15)70115-4 Pignata et al. 2015 (MITO 11)]
+|2010-2013
+|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+|[[#Paclitaxel_monotherapy_2|Paclitaxel]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 6.35 vs 3.49 mo<br>(HR 0.42, 95% CI 0.25-0.69)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+====Targeted therapy====
+*[[Pazopanib (Votrient)]] 800 mg PO once per day on days 1 to 28, taken at least 2 hours after or 1 hour before eating
 '''28-day cycles'''
+</div></div>
 ===References===
-# Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. Epub 2010 Jul 6. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960893-8/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20609468 PubMed]
+# '''MITO 11:''' Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. [https://doi.org/10.1016/S1470-2045(15)70115-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25882986/ PubMed] [https://clinicaltrials.gov/study/NCT01644825 NCT01644825]
-# Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. Epub 2011 Aug 19. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970214-5/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21862407 PubMed]
+==Pazopanib monotherapy {{#subobject:86404d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Paclitaxel (Taxol)==
+===Regimen {{#subobject:ce993f|Variant=1}}===
-===Regimen, Gynecologic Oncology Group et al. 2006; Pujade-Lauraine et al. 2014 (AURELIA); Stockler et al. 2014 (AURELIA)===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-Level of Evidence:
+!style="width: 33%"|Study
-<span
+!style="width: 33%"|Dates of enrollment
-style="background:#EEEE00;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-padding:3px 6px 3px 6px;
+|-
-border-color:black;
+|[https://doi.org/10.1016/j.ygyno.2010.05.033 Friedlander et al. 2010]
-border-width:2px;
+|Not reported
-border-style:solid;">Phase II</span>
+|style="background-color:#91cf61"|Phase 2
+|-
-*[[Paclitaxel (Taxol)]] 80 mg/m2 IV over 1 hour once per day on days 1, 8, 15, 22
+|}
-*Body surface area capped at 2 m2
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Pazopanib (Votrient)]] 800 mg PO once per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
+===References===
+# Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, Ma B, Hodge JP, Lager JJ. A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010 Oct;119(1):32-7. Epub 2010 Jun 27. [https://doi.org/10.1016/j.ygyno.2010.05.033 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20584542/ PubMed]
+==Pegylated liposomal doxorubicin monotherapy {{#subobject:cd6479|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 40 mg/m<sup>2</sup> {{#subobject:3cc773|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5318972/ Lindemann et al. 2017 (Ovaresist)]
+|2002-2007
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Tamoxifen_monotherapy_999|Tamoxifen]]
+|style="background-color:#1a9850"|Superior PFS
+|-
+|[https://doi.org/10.1200/jco.2007.13.6606 Ferrandina et al. 2008 (MITO-3)]
+|2003-2007
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Gemcitabine_monotherapy|Gemcitabine]]
+|style="background-color:#fee08b"|Might have inferior ORR (secondary endpoint)
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]<br>1b. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>1c. [[#Topotecan_.26_Bevacizumab|Topotecan & Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7767649/ Motohashi et al. 2020 (JGOG 3018)]
+|2010-2017
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]; 50 mg/m<sup>2</sup>
+|style="background-color:#ffffbf"|Inconclusive whether non-inferior PFS (primary endpoint)
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00216-3 Pujade-Lauraine et al. 2021 (JAVELIN Ovarian 200)]
+|2016-01-05 to 2017-05-16
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Avelumab_monotherapy_999|Avelumab]]<br>2. [[#Pegylated_liposomal_doxorubicin_.26_Avelumab_999|PLD & Avelumab]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS
+|-
+|[https://doi.org/10.1016/j.annonc.2021.02.017 Moore et al. 2021 (FORWARD I)]
+|2017-01-24 to 2018-04-23
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1056/nejmoa2309169 Moore et al. 2023 (MIRASOL)]
+|2020-02-03 to NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04679064 Awaiting publication (NItCHE)]
+|2020-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Niraparib_.26_Dostarlimab_666|Niraparib & Dostarlimab]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of OS
+|-
+|}
+''Note: Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*FORWARD I & MIRASOL: High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Supportive therapy====
+*[[Methylprednisolone (Solumedrol)]] 20 mg IV once on day 1; 30 minutes prior to pegylated liposomal doxorubicin
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 50 mg/m<sup>2</sup> {{#subobject:8dcbc1|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1997.15.3.987 Muggia et al. 1997]
+|1994-1995
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.2000.18.17.3093 Gordon et al. 2000]
+|Not reported-1998
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/jco.2001.19.14.3312 Gordon et al. 2001 (Doxil Study 30-49)]
+|1997-1999
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
+|[[#Topotecan_monotherapy|Topotecan]]
+|style="background-color:#d9ef8b"|Might have superior PFS (co-primary endpoint)
+|-
+|[https://doi.org/10.1200/jco.2006.09.6735 Mutch et al. 2007 (B9E-US-S301)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Gemcitabine_monotherapy|Gemcitabine]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/j.ejca.2009.05.016 Vergote et al. 2009 (ASSIST-1)]
+|2003-2006
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Canfosfamide_monotherapy_999|Canfosfamide]]
+|style="background-color:#1a9850"|Superior OS
+|-
+|[https://clinicaltrials.gov/study/NCT00102973 Awaiting publication (ASSIST-3)]
+|2004-2008
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Canfosfamide_.26_Carboplatin_999|Canfosfamide & Carboplatin]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/JCO.2009.25.4037 Monk et al. 2010 (OVA-301)]
+|2005-2007
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_.26_Trabectedin|PLD & Trabectedin]]
+| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
+|-
+|[https://doi.org/10.1200/JCO.2011.38.8082 Colombo et al. 2012 (CEPO906A2303)]
+|2005-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Patupilone_monotherapy_999|Patupilone]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1111/igc.0b013e3181daaf59 Vergote et al. 2010 (ASSIST-5)]
+|2006-09 to 2007-06
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Canfosfamide_.26_Pegylated_liposomal_doxorubicin_999|Canfosfamide & PLD]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7767649/ Motohashi et al. 2020 (JGOG 3018)]
+|2010-2017
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]; 40 mg/m<sup>2</sup>
+|style="background-color:#ffffbf"|Inconclusive whether non-inferior PFS
+|-
+|[https://doi.org/10.1016/j.ejca.2016.09.004 Marth et al. 2016 (TRINOVA-2)]
+|2011-2013
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Stub#Pegylated_liposomal_doxorubicin_.26_Trebananib|PLD & Trebananib]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS<br>Median PFS: 7.2 vs 7.6 mo<br>(HR 1.09, 95% CI 0.81-1.47)
+|-
+|[https://doi.org/10.1016/j.ygyno.2019.12.043 Monk et al. 2020 (CR100983)]
+|2013-2018
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_.26_Trabectedin|PLD & Trabectedin]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<br>Median OS: 22.2 vs 23.8 mo<br>(HR 1.09, 95% CI 0.85-1.37)
+|-
+|[https://doi.org/10.1016/j.ygyno.2021.08.032 Gaillard et al. 2021 (CORAIL)]
+|2015-06-26 to 2018-10-12
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Lurbinectedin_monotherapy_999|Lurbinectedin]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS<br>Median PFS: 3.6 vs 3.5 mo<br>(HR 0.95)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601279/ Hamanishi et al. 2021 (NINJA)]
+|2015-10-07 to 2017-12-21
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Nivolumab_monotherapy_999|Nivolumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<br>Median OS: 12.1 vs 10.1 mo<br>(HR 1.00, 95% CI 0.77-1.25)
+|-
+|}
+''<sup>1</sup>Reported efficacy for OVA-301 is based on the 2012 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Pegylated liposomal doxorubicin (Doxil)]] 50 mg/m<sup>2</sup> IV over 60 to 90 minutes once on day 1
 '''28-day cycles'''
+</div></div>
-Supportive medications:
-*[[Dexamethasone (Decadron)]] 10 mg PO/IV once 30 to 60 minutes prior to paclitaxel
-*Diphenhydramine (Benadryl) 25 to 50 mg IV once 30 to 60 minutes prior to paclitaxel
-*H2 blocker 30 to 60 minutes prior to paclitaxel
 ===References===
-# Gynecologic Oncology Group, Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jun;101(3):436-40. Epub 2005 Dec 2. [http://www.sciencedirect.com/science/article/pii/S0090825805009765 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16325893 PubMed]
+# Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang LJ. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987-93. [https://doi.org/10.1200/JCO.1997.15.3.987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9060537/ PubMed]
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+# Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Rosales R, Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3093-100. [https://doi.org/10.1200/JCO.2000.18.17.3093 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963637/ PubMed]
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+# '''Doxil Study 30-49:''' Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. [https://doi.org/10.1200/jco.2001.19.14.3312 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11454878/ PubMed]
+## '''Update:''' Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. [https://doi.org/10.1016/j.ygyno.2004.07.011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15385103/ PubMed]
+<!-- Presented in part at the 29th European Congress on Clinical Oncology, October 30-November 3, 2005, Paris, France; and at the 37th Annual Meeting of the Society of Gynecologic Oncologists, March 22-26, 2006, Palm Springs, CA. -->
+# '''B9E-US-S301:''' Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. [https://doi.org/10.1200/jco.2006.09.6735 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17602086/ PubMed] content property of [https://hemonc.org HemOnc.org] [https://clinicaltrials.gov/study/NCT00191607 NCT00191607]
+# '''MITO-3:''' Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. [https://doi.org/10.1200/jco.2007.13.6606 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18281662/ PubMed]
+# '''ASSIST-1:''' Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Kavanagh J, Vermorken JB, Meng L, Jones M, Brown G, Kaye S; ASSIST-1 Study Group. Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. Eur J Cancer. 2009 Sep;45(13):2324-32. Epub 2009 Jun 8. [https://doi.org/10.1016/j.ejca.2009.05.016 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19515553/ PubMed] [https://clinicaltrials.gov/study/NCT00057720 NCT00057720]
+<!-- # '''Abstract:''' I. Vergote, N. J. Finkler, J. B. Hall, O. Melnyk, R. P. Edwards, M. Jones, L. Meng, G. L. Brown, E. M. Rankin, J. J. Burke II, and P. G. Rose. Randomized phase III study of canfosfamide (C, TLK286) plus pegylated liposomal doxorubicin (PLD) versus PLD as second-line therapy in platinum (P) refractory or resistant ovarian cancer (OC). Journal of Clinical Oncology 2009 27:15S, 5552-5552 [https://doi.org/10.1200/jco.2009.27.15s.5552 link to abstract] -->
+# '''ASSIST-5:''' Vergote I, Finkler NJ, Hall JB, Melnyk O, Edwards RP, Jones M, Keck JG, Meng L, Brown GL, Rankin EM, Burke JJ, Boccia RV, Runowicz CD, Rose PG. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2010 Jul;20(5):772-80. [https://doi.org/10.1111/igc.0b013e3181daaf59 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20973267/ PubMed] [https://clinicaltrials.gov/study/NCT00350948 NCT00350948]
+# '''OVA-301:''' Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. [https://doi.org/10.1200/JCO.2009.25.4037 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20516432/ PubMed] [https://clinicaltrials.gov/study/NCT00113607 NCT00113607]
+##'''PRO analysis:''' Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. [https://doi.org/10.1016/j.ygyno.2012.06.034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22765965/ PubMed]
+## '''Update:''' Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. [https://doi.org/10.1016/j.ejca.2012.04.001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22541893/ PubMed]
+# '''CEPO906A2303:''' Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, Scambia G, Engelholm SA, Joly F, Weber D, El-Hashimy M, Li J, Souami F, Wing P, Engelholm S, Bamias A, Schwartz P. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. J Clin Oncol. 2012 Nov 1;30(31):3841-7. Epub 2012 Sep 17. [https://doi.org/10.1200/JCO.2011.38.8082 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22987083/ PubMed] [https://clinicaltrials.gov/study/NCT00262990 NCT00262990]
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
+# '''TRINOVA-2:''' Marth C, Vergote I, Scambia G, Oberaigner W, Clamp A, Berger R, Kurzeder C, Colombo N, Vuylsteke P, Lorusso D, Hall M, Renard V, Pignata S, Kristeleit R, Altintas S, Rustin G, Wenham RM, Mirza MR, Fong PC, Oza A, Monk BJ, Ma H, Vogl FD, Bach BA. ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer. Eur J Cancer. 2017 Jan;70:111-121. Epub 2016 Dec 1. [https://doi.org/10.1016/j.ejca.2016.09.004 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27914241/ PubMed] [https://clinicaltrials.gov/study/NCT01281254 NCT01281254]
+# '''Ovaresist:''' Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. [https://doi.org/10.1038/bjc.2016.435 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5318972/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28118323/ PubMed] [https://clinicaltrials.gov/study/NCT02728622 NCT02728622]
+# '''CR100983:''' Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. Epub 2020 Jan 8. [https://doi.org/10.1016/j.ygyno.2019.12.043 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31924332/ PubMed] [https://clinicaltrials.gov/study/NCT01846611 NCT01846611]
+#'''JGOG 3018:''' Motohashi T, Yabuno A, Michimae H, Ohishi T, Nonaka M, Takano M, Nishio S, Fujiwara H, Fujiwara K, Kondo E, Sugiyama T, Tabata T. Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial. J Gynecol Oncol. 2021 Jan;32(1):e9. Epub 2020 Nov 10. [https://doi.org/10.3802/jgo.2021.32.e9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7767649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33185050/ PubMed] UMIN000003130
+# '''FORWARD I:''' Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. [https://doi.org/10.1016/j.annonc.2021.02.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33667670/ PubMed] [https://clinicaltrials.gov/study/NCT02631876 NCT02631876]
+# '''JAVELIN Ovarian 200:''' Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, Richardson GE, Sessa C, Yonemori K, Banerjee S, Leary A, Tinker AV, Jung KH, Madry R, Park SY, Anderson CK, Zohren F, Stewart RA, Wei C, Dychter SS, Monk BJ. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021 Jul;22(7):1034-1046. Epub 2021 Jun 15. [https://doi.org/10.1016/s1470-2045(21)00216-3 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34143970/ PubMed] [https://clinicaltrials.gov/study/NCT02580058 NCT02580058]
+#'''NINJA:''' Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. [https://doi.org/10.1200/jco.21.00334 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601279/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34473544/ PubMed] JapicCTI-153004
+#'''CORAIL:''' Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. [https://doi.org/10.1016/j.ygyno.2021.08.032 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34521554/ PubMed] [https://clinicaltrials.gov/study/NCT02421588 NCT02421588]
+#'''MIRASOL:''' Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. [https://doi.org/10.1056/nejmoa2309169 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38055253/ PubMed] [https://clinicaltrials.gov/study/NCT04209855 NCT04209855]
+# '''AGO-OVAR 2.29:''' [https://clinicaltrials.gov/study/NCT03353831 NCT03353831]
+# '''ARTISTRY-7:''' [https://clinicaltrials.gov/study/NCT05092360 NCT05092360]
+# '''ASSIST-3:''' [https://clinicaltrials.gov/study/NCT00102973 NCT00102973]
+# '''EPIK-O:''' [https://clinicaltrials.gov/study/NCT04729387 NCT04729387]
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
+# '''PROCEED<sub>OV</sub>:''' [https://clinicaltrials.gov/study/NCT01170650 NCT01170650]
-==Paclitaxel & Bevacizumab==
+==Pegylated liposomal doxorubicin & Bevacizumab {{#subobject:c059ce|Regimen=1}}==
-===Regimen, Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA)===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen {{#subobject:707619|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-style="background:#00CD00;
+!style="width: 20%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Dates of enrollment
-border-color:black;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+!style="width: 20%"|Comparator
-border-style:solid;">Phase III</span>
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-*[[Paclitaxel (Taxol)]] 80 mg/m2 IV once per day on days 1, 8, 15, 22
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-37-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 6.7 vs 3.4 mo<br>(HR 0.48, 95% CI 0.38-0.60)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
 *[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
+'''28-day cycles'''
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+</div></div>
 ===References===
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
-==Paclitaxel, nanoparticle albumin-bound (Abraxane)==
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
-===Regimen, Teneriello et al. 2009===
+==Pegylated liposomal doxorubicin & Trabectedin {{#subobject:edac44|Regimen=1}}==
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen {{#subobject:1e385c|Variant=1}}===
-style="background:#EEEE00;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Study
-border-color:black;
+!style="width: 20%"|Dates of enrollment
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase II</span>
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m2 IV over 30 minutes once on day 1
+|-
+|[https://doi.org/10.1200/JCO.2009.25.4037 Monk et al. 2010 (OVA-301)]
-'''21-day cycles x 6 to 8 cycles'''
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-45-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+|-
+|} -->
+|2005-2007
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
+| style="background-color:#d9ef8b" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 7.3 vs 5.8 mo<br>(HR 0.79, 95% CI 0.65-0.96)<br><br>Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 22.2 vs 18.9 mo<br>(HR 0.86, 95% CI 0.72-1.02)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2012 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
+*[[Trabectedin (Yondelis)]] 1.1 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second, 30 minutes later'''
+'''21-day cycles'''
+</div></div>
 ===References===
-# Teneriello MG, Tseng PC, Crozier M, Encarnacion C, Hancock K, Messing MJ, Boehm KA, Williams A, Asmar L. Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009 Mar 20;27(9):1426-31. Epub 2009 Feb 17. [http://jco.ascopubs.org/content/27/9/1426.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19224848 PubMed]
+# '''OVA-301:''' Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. [https://doi.org/10.1200/JCO.2009.25.4037 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20516432/ PubMed] [https://clinicaltrials.gov/study/NCT00113607 NCT00113607]
+##'''PRO analysis:''' Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. [https://doi.org/10.1016/j.ygyno.2012.06.034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22765965/ PubMed]
-==Pazopanib (Votrient)==
+## '''Update:''' Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. [https://doi.org/10.1016/j.ejca.2012.04.001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22541893/ PubMed]
-===Regimen, Friedlander et al. 2010===
+==Pemetrexed monotherapy {{#subobject:5baa02|Regimen=1}}==
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen variant #1, 700 mg/m<sup>2</sup> {{#subobject:4e32e8|Variant=1}}===
-style="background:#EEEE00;
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 33%"|Study
-border-color:black;
+!style="width: 33%"|Dates of enrollment
-border-width:2px;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase II</span>
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690393/ Miller et al. 2009 (GOG-0126Q)]
-*[[Pazopanib (Votrient)]] 800 mg PO once per day
+|2004-2006
+|style="background-color:#91cf61"|Phase 2
-'''given until progression of disease or unacceptable toxicity'''
+|-
+|}
-===References===
+''Note: this is the dosage for patients with previous radiation therapy.''
-# Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, Ma B, Hodge JP, Lager JJ. A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010 Oct;119(1):32-7. doi: 10.1016/j.ygyno.2010.05.033. Epub 2010 Jun 27. [http://www.sciencedirect.com/science/article/pii/S0090825810004257 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20584542 PubMed]
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-==Pemetrexed (Alimta)==
+*[[Pemetrexed (Alimta)]] 700 mg/m<sup>2</sup> IV over 10 minutes once on day 1
-===Regimen, Miller et al. 2009===
+====Supportive therapy====
-Level of Evidence:
+*Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
-<span
+*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
-style="background:#EEEE00;
+*[[Dexamethasone (Decadron)]] 4 mg PO twice per day the day before, the day of, and day after pemetrexed
-padding:3px 6px 3px 6px;
+*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Pemetrexed (Alimta)]] 900 mg/m2 IV over 10 minutes once on day 1
-**Dosage for patients with previous radiation therapy was [[Pemetrexed (Alimta)]] 700 mg/m2 IV over 10 minutes once on day 1
 '''21-day cycles'''
+</div></div><br>
-Supportive medications:
+<div class="toccolours" style="background-color:#eeeeee">
-*Folic acid 350 to 600 mcg PO once per day, starting 7 days before pemetrexed, to continue throughout therapy
+===Regimen variant #2, 900 mg/m<sup>2</sup> {{#subobject:4e68e8|Variant=1}}===
-*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once 7 days before pemetrexed (then 1000 mcg to be given once every 9 weeks thereafter)
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-*[[Dexamethasone (Decadron)]] 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta)
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690393/ Miller et al. 2009 (GOG-0126Q)]
+|2004-2006
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Pemetrexed (Alimta)]] 900 mg/m<sup>2</sup> IV over 10 minutes once on day 1
+====Supportive therapy====
+*Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
+*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
+*[[Dexamethasone (Decadron)]] 4 mg PO twice per day the day before, the day of, and day after pemetrexed
 *No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
+'''21-day cycles'''
+</div></div>
 ===References===
-# Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009 Jun 1;27(16):2686-91. Epub 2009 Mar 30. [http://jco.ascopubs.org/content/27/16/2686.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19332726 PubMed]
+# '''GOG-0126Q:''' Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH; Gynecologic Oncology Group. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009 Jun 1;27(16):2686-91. Epub 2009 Mar 30. [https://doi.org/10.1200/jco.2008.19.2963 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19332726/ PubMed] [https://clinicaltrials.gov/study/NCT00087087 NCT00087087]
+==Topotecan monotherapy {{#subobject:7dbd5a|Regimen=1}}==
-==Topotecan (Hycamtin)==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #1, Gordon et al. 2004===
+===Regimen variant #1, 4 mg/m<sup>2</sup>, 3 weeks out of 4 x 12 mo {{#subobject:a8bc04|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1200/jco.2009.27.8911 Sehouli et al. 2010 (TOWER<sub>ov</sub>)]
-*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
+|2005-2008
+|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
+|[[#Topotecan_monotherapy|Topotecan]]; q3wk
+|style="background-color:#ffffbf"|Did not meet primary endpoint of CBR
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]<br>1b. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>1c. [[#Topotecan_.26_Bevacizumab|Topotecan & Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|}
+''Note: TOWER should not be confused with the trial by the same name in B-ALL.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 4 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
+'''28-day cycle for up to 13 cycles (1 year)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 4 mg/m<sup>2</sup>, 3 weeks out of 4, indefinite {{#subobject:b9bc04|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]<br>1b. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>1c. [[#Topotecan_.26_Bevacizumab|Topotecan & Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1016/j.annonc.2021.02.017 Moore et al. 2021 (FORWARD I)]
+|2017-01-24 to 2018-04-23
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1056/nejmoa2309169 Moore et al. 2023 (MIRASOL)]
+|2020-02-03 to NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*FORWARD I & MIRASOL: High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 4 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 6.25 mg/m<sup>2</sup>, split dosing, q3wk x 12 mo {{#subobject:a6c302|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2009.27.8911 Sehouli et al. 2010 (TOWER<sub>ov</sub>)]
+|2005-2008
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Topotecan_monotherapy|Topotecan]]; weekly
+|style="background-color:#ffffbf"|Did not meet primary endpoint of CBR
+|-
+|}
+''Note: TOWER should not be confused with the trial by the same name in B-ALL.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 1.25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+'''21-day cycle for up to 18 cycles (1 year)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 6.25 mg/m<sup>2</sup>, split dosing, q3wk, indefinite {{#subobject:b7c302|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2007.15.1258 Sehouli et al. 2008]
+|1999-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Etoposide_.26_Topotecan_999|Etoposide & Topotecan]]<br>2. [[#Gemcitabine_.26_Topotecan_999|Gemcitabine & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2009.04.026 Meier et al. 2009 (AGO-OVAR 2.3)]
+|1998-2002
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Treosulfan_monotherapy|Treosulfan]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]<br>1b. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>1c. [[#Topotecan_.26_Bevacizumab|Topotecan & Bevacizumab]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|[https://doi.org/10.1200/jco.2015.66.0787 Kurzeder et al. 2016 (PENELOPE)]
+|2013-10-02 to 2014-09-18
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Gemcitabine_.26_Pertuzumab_999|Gemcitabine & Pertuzumab]]<br>1b. [[#Paclitaxel_.26_Pertuzumab_999|Paclitaxel & Pertuzumab]]<br>1c. [[#Topotecan_.26_Pertuzumab_999|Topotecan & Pertuzumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/j.annonc.2021.02.017 Moore et al. 2021 (FORWARD I)]
+|2017-01-24 to 2018-04-23
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1056/nejmoa2309169 Moore et al. 2023 (MIRASOL)]
+|2020-02-03 to NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Mirvetuximab_soravtansine_monotherapy|Mirvetuximab soravtansine]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04679064 Awaiting publication (NItCHE)]
+|2020-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Niraparib_.26_Dostarlimab_666|Niraparib & Dostarlimab]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of OS
+|-
+|}
+''Note: this was the dosing used in third-line therapy in AGO-OVAR 2.3.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*FORWARD I & MIRASOL: High folate receptor-alpha expression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 1.25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 7.5 mg/m<sup>2</sup>, split dosing, q3wk {{#subobject:2bf80a|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1998.16.10.3345 Bookman et al. 1996]
+|Not reported
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.1997.15.6.2183 ten Bokkel Huinink et al. 1997]
+|Not reported
+|style="background-color:#1a9851"|Randomized (E-RT-switch-ic)
+|[[#Paclitaxel_monotherapy_2|Paclitaxel]]
+| style="background-color:#d9ef8b" |Might have superior TTP<sup>1</sup> (co-primary endpoint)
+|-
+|[https://doi.org/10.1200/jco.2001.19.14.3312 Gordon et al. 2001 (Doxil Study 30-49)]
+|1997-1999
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
+|style="background-color:#fee08b"|Might have inferior PFS
+|-
+|[https://doi.org/10.1016/j.ygyno.2009.04.026 Meier et al. 2009 (AGO-OVAR 2.3)]
+|1998-2002
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Treosulfan_monotherapy|Treosulfan]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2021.08.032 Gaillard et al. 2021 (CORAIL)]
+|2015-06-26 to 2018-10-12
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Lurbinectedin_monotherapy_999|Lurbinectedin]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS<br>Median PFS: 3.6 vs 3.5 mo<br>(HR 0.95)
+|-
+|}
+''<sup>1</sup>Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.''<br>
+''Note: this was the dosing used in second-line therapy in AGO-OVAR 2.3.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 '''21-day cycles'''
+</div></div>
-===Regimen #2, Sehouli et al. 2011; Pujade-Lauraine et al. 2014 (AURELIA); Stockler et al. 2014 (AURELIA)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II, >20 per arm</span>
-*[[Topotecan (Hycamtin)]] 1.25 mg/m2 IV over 30 minutes once per day on days 1 to 5
-'''21-day cycles x up to 12 months'''; in Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA), topotecan was given until progression of disease or unacceptable toxicity
-===Regimen #3, Sehouli et al. 2011 (weekly topotecan); Pujade-Lauraine et al. 2014 (AURELIA); Stockler et al. 2014 (AURELIA)===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II, >20 per arm</span>
-*[[Topotecan (Hycamtin)]] 4 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
-'''28-day cycles x up to 12 months'''; in Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA), topotecan was given until progression of disease or unacceptable toxicity
 ===References===
-# Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. [http://www.sciencedirect.com/science/article/pii/S0090825804005232 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15385103 PubMed]
+# Bookman MA, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs JB, Fields SZ. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol. 1998 Oct;16(10):3345-52. [https://doi.org/10.1200/JCO.1998.16.10.3345 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9779711/ PubMed]
-# Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, Markmann S, Mahner S, Mueller L, Lorenz R, Nugent A, Wilke J, Kuznik A, Doering G, Wischnik A, Sommer H, Meerpohl HG, Schroeder W, Lichtenegger W, Oskay-Oezcelik G. Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2011 Jan 10;29(2):242-8. Epub 2010 Nov 29. [http://jco.ascopubs.org/content/29/2/242.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21115872 PubMed]
+# ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. [https://doi.org/10.1200/JCO.1997.15.6.2183 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9196130/ PubMed]
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+## '''Update:''' ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. [https://doi.org/10.1093/annonc/mdh025 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14679127/ PubMed]
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+# '''Doxil Study 30-49:''' Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. [https://doi.org/10.1200/jco.2001.19.14.3312 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11454878/ PubMed]
+## '''Update:''' Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. [https://doi.org/10.1016/j.ygyno.2004.07.011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15385103/ PubMed]
+# Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2008 Jul 1;26(19):3176-82. [https://doi.org/10.1200/jco.2007.15.1258 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18591555/ PubMed]
+# '''AGO-OVAR 2.3:''' Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. [https://doi.org/10.1016/j.ygyno.2009.04.026 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19446314/ PubMed]
+<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
+# '''TOWER:''' Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, Markmann S, Mahner S, Mueller L, Lorenz R, Nugent A, Wilke J, Kuznik A, Doering G, Wischnik A, Sommer H, Meerpohl HG, Schroeder W, Lichtenegger W, Oskay-Oezcelik G; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2011 Jan 10;29(2):242-8. Epub 2010 Nov 29. [https://doi.org/10.1200/jco.2009.27.8911 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21115872/ PubMed] [https://clinicaltrials.gov/study/NCT00170677 NCT00170677]
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
+<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
+# '''PENELOPE:''' Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. [https://doi.org/10.1200/jco.2015.66.0787 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27269942/ PubMed] [https://clinicaltrials.gov/study/NCT01684878 NCT01684878]
+## '''Update:''' Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. [https://doi.org/10.1136/ijgc-2019-000370 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31420414/ PubMed]
+# '''FORWARD I:''' Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. [https://doi.org/10.1016/j.annonc.2021.02.017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33667670/ PubMed] [https://clinicaltrials.gov/study/NCT02631876 NCT02631876]
+#'''CORAIL:''' Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. [https://doi.org/10.1016/j.ygyno.2021.08.032 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34521554/ PubMed] [https://clinicaltrials.gov/study/NCT02421588 NCT02421588]
+#'''MIRASOL:''' Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. [https://doi.org/10.1056/nejmoa2309169 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38055253/ PubMed] [https://clinicaltrials.gov/study/NCT04209855 NCT04209855]
+# '''DOXILOVC3001:''' [https://clinicaltrials.gov/study/NCT01840943 NCT01840943]
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
-==Topotecan & Bevacizumab==
+==Topotecan & Bevacizumab {{#subobject:7994da|Regimen=1}}==
-===Regimen #1, Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA)===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen variant #1, topotecan 3 weeks out of 4 {{#subobject:5a9474|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-style="background:#00CD00;
+!style="width: 20%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Dates of enrollment
-border-color:black;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+!style="width: 20%"|Comparator
-border-style:solid;">Phase III</span>
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-*[[Topotecan (Hycamtin)]] 4 mg/m2 IV once per day on days 1, 8, 15
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-37-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 6.7 vs 3.4 mo<br>(HR 0.48, 95% CI 0.38-0.60)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 4 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+====Targeted therapy====
 *[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
+'''28-day cycles'''
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #2, Pujade-Lauraine et al. 2014 (AURELIA) & Stockler et al. 2014 (AURELIA)===
+===Regimen variant #2, topotecan 6.25 mg/m<sup>2</sup>, split dosing, q3wk {{#subobject:352c9e|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1200/jco.2013.51.4489 Pujade-Lauraine et al. 2014 (AURELIA)]
-*[[Topotecan (Hycamtin)]] 1.25 mg/m2 IV once per day on days 1 to 5
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-37-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2009-2011
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Paclitaxel_monotherapy_2|Paclitaxel]]<br>1b. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1c. [[#Topotecan_monotherapy|Topotecan]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 6.7 vs 3.4 mo<br>(HR 0.48, 95% CI 0.38-0.60)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] 1.25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+====Targeted therapy====
 *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles'''
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+</div></div>
+===References===
+# '''AURELIA:''' Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.4489 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24637997/ PubMed] [https://clinicaltrials.gov/study/NCT00976911 NCT00976911]
+## '''PRO analysis:''' Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.51.4240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876313/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687829/ PubMed]
+## '''Subgroup analysis:''' Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. [https://doi.org/10.1016/j.ygyno.2016.11.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27871723/ PubMed]
+# '''NItCHE:''' [https://clinicaltrials.gov/study/NCT04679064 NCT04679064]
+==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:33de2b|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360276/ Krasner et al. 2007]
+|2002-2004
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Trabectedin (Yondelis)]] 0.58 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 8, 15
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 10 mg IV once per day on days 1, 8, 15, '''given 30 minutes prior to chemotherapy'''
+'''28-day cycles'''
+</div></div>
+===References===
+# Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, Provencher DM, Campos S, Gore ME. A phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007 Dec 17;97(12):1618-24. Epub 2007 Nov 13. [https://doi.org/10.1038/sj.bjc.6604088 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360276/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18000504/ PubMed]
+==Treosulfan monotherapy {{#subobject:b8b3ed|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:22ce2b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2009.04.026 Meier et al. 2009 (AGO-OVAR 2.3)]
+|1998-2002
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Topotecan_monotherapy|Topotecan]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306340/ Sehouli et al. 2016]
+|2002-2014
+|style="background-color:#1a9851"|Phase 3b (C)
+|[[#Treosulfan_monotherapy|Treosulfan]]; PO
+| style="background-color:#d9ef8b" |Might have superior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Treosulfan (Ovastat)]] by the following renal function-based criteria:
+**CrCl more than 40 mL/min/1.73 m<sup>2</sup>: 7000 mg/m<sup>2</sup> IV once on day 1
+**CrCl 20 to 40 mL/min/1.73 m<sup>2</sup>: 6000 mg/m<sup>2</sup> IV once on day 1
+**CrCl less than 20 mL/min/1.73 m<sup>2</sup>: 5000 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycles'''
+</div></div>
 ===References===
-# Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. [http://jco.ascopubs.org/content/32/13/1302.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24637997 PubMed]
+# '''AGO-OVAR 2.3:''' Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. [https://doi.org/10.1016/j.ygyno.2009.04.026 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19446314/ PubMed]
-# Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. [http://jco.ascopubs.org/content/32/13/1309.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24687829 PubMed]
+# Sehouli J, Tomè O, Dimitrova D, Camara O, Runnebaum IB, Tessen HW, Rautenberg B, Chekerov R, Muallem MZ, Lux MP, Trarbach T, Gitsch G. A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO). J Cancer Res Clin Oncol. 2017 Mar;143(3):541-550. Epub 2016 Nov 28. [https://doi.org/10.1007/s00432-016-2307-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306340/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27896440/ PubMed]
+==Vinorelbine monotherapy {{#subobject:4884ac|Regimen=1}}==
-==Vinorelbine (Navelbine)==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen, Rothenberg et al. 2004===
+===Regimen {{#subobject:9e623e|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-<span
+!style="width: 33%"|Study
-style="background:#EEEE00;
+!style="width: 33%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+|-
-border-width:2px;
+|[https://doi.org/10.1016/j.ygyno.2004.09.004 Rothenberg et al. 2004]
-border-style:solid;">Phase II</span>
+|1995-03 to 1997-07
+|style="background-color:#91cf61"|Phase 2
-*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV once per day on days 1 & 8
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
 ===References===
-# Rothenberg ML, Liu PY, Wilczynski S, Nahhas WA, Winakur GL, Jiang CS, Moinpour CM, Lyons B, Weiss GR, Essell JH, Smith HO, Markman M, Alberts DS. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004 Dec;95(3):506-12. [http://www.sciencedirect.com/science/article/pii/S0090825804007073 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15581954 PubMed]
+# Rothenberg ML, Liu PY, Wilczynski S, Nahhas WA, Winakur GL, Jiang CS, Moinpour CM, Lyons B, Weiss GR, Essell JH, Smith HO, Markman M, Alberts DS; [[Study_Groups#SWOG|SWOG]]. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004 Dec;95(3):506-12. [https://doi.org/10.1016/j.ygyno.2004.09.004 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15581954/ PubMed]
-[[Category:Chemotherapy regimens]]
+[[Category:Ovarian cancer regimens]]
-[[Category:Solid oncology regimens]]
+[[Category:Disease-specific pages]]
-[[Category:Gynecologic oncology regimens]]
+[[Category:Gynecologic cancers]]

Difference between revisions of "Ovarian cancer"

Latest revision as of 12:11, 23 July 2024

Guidelines

ASCO

ESMO

ESMO/ESGO/ESP

NCCN

SGO/ASCO

Adjuvant therapy for early stage disease

Carboplatin monotherapy

Regimen variant #1, AUC 5

Preceding treatment

Chemotherapy

Regimen variant #2, 350 mg/m2

Preceding treatment

Chemotherapy

References

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 6/175

Preceding treatment

Chemotherapy

Subsequent treatment

Regimen variant #2, 7.5/175

Preceding treatment

Chemotherapy

References

Neoadjuvant chemotherapy for advanced stage disease

Carboplatin & Paclitaxel (CP)

Regimen variant #1, AUC 5/175 x 3

Chemotherapy

Subsequent treatment

Regimen variant #2, AUC 5/175 x 6

Chemotherapy

Subsequent treatment

Regimen variant #3, AUC 6/175 x 3

Chemotherapy

Subsequent treatment

References

First-line chemotherapy for advanced stage disease

Carboplatin monotherapy

Regimen variant #1, AUC 5

Chemotherapy

Regimen variant #2, AUC 6, q3wk

Chemotherapy

Regimen variant #3, AUC 6, q4wk

Chemotherapy

Regimen variant #4, AUC 9

Preceding treatment

Chemotherapy

Subsequent treatment

Regimen variant #5, 400 mg/m2, q4wk

Chemotherapy

References

Carboplatin & Docetaxel

Regimen

Preceding treatment

Chemotherapy

Supportive therapy

References

Carboplatin & Pegylated liposomal doxorubicin

Regimen

Preceding treatment

Chemotherapy

Supportive therapy

References

Carboplatin & Gemcitabine (GCb)

Regimen

Chemotherapy

Subsequent treatment

References

Carboplatin & Paclitaxel (CP)

Regimen variant #1, q1wk AUC 2/60

Chemotherapy

Regimen variant #2, q3wk AUC 5, q1wk 80

Chemotherapy

Regimen variant #3, q3wk AUC 5/175

Preceding treatment

Chemotherapy

Supportive therapy

Regimen variant #4, q3wk AUC 6, q1wk 80

Regimen variant #2, 350 mg/m²

Regimen variant #5, 400 mg/m², q4wk