Ovarian cancer

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Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (C) 1a. CP & Nivolumab
1b. CVb & Nivolumab
1c. DC & Nivolumab 		Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02998528

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Section editor
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 Brandon L. Seagle, MD, MS
Chicago, IL
51 regimens on this page
98 variants on this page


Guidelines

ESMO

NCCN

First-line chemotherapy for advanced/metastatic disease

Carboplatin & Docetaxel

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Regimen

Study Evidence Comparator Efficacy
Vasey et al. 2004 Phase III Carboplatin & Paclitaxel Seems not superior

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  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 contains verified protocol PubMed

Carboplatin & Doxorubicin liposomal

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Regimen

Study Evidence Comparator Efficacy
Pignata et al. 2006 (MITO-2) Phase III Carboplatin & Paclitaxel Seems not superior

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).

Chemotherapy

Supportive medications

  • "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

  1. 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. contains verified protocol link to PMC article PubMed
    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 contains verified protocol PubMed

Carboplatin & Gemcitabine

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Regimen

Study Evidence Comparator Efficacy
Gordon et al. 2011 Phase III Carboplatin & Paclitaxel Seems not superior

Chemotherapy

21-day cycle for up to 6 cycles

Patients with complete response could optionally proceed to receive paclitaxel consolidation.

References

  1. 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 contains verified protocol PubMed

Carboplatin & Paclitaxel

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TC: Taxol (Paclitaxel), Carboplatin

Regimen #1, q1wk AUC 2/60

Study Evidence Comparator Efficacy
Pignata et al. 2014 (MITO-7) Phase III TC, q3wk AUC 6/175 Seems not superior

Chemotherapy

18-week course

Regimen #2, q3wk AUC 5/175

Study Evidence Comparator Efficacy
Vasey et al. 2004 Phase III Carboplatin & Docetaxel Seems not superior
Pignata et al. 2006 (MITO-2) Phase III Carboplatin & Pegylated liposomal doxorubicin Seems not superior
du Bois et al. 2015 (AGO-OVAR 12) Phase III Carboplatin, Nintedanib, Paclitaxel Seems to have inferior PFS

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

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

Regimen #3, q3wk AUC 6, q1wk 80 ("dose-dense")

Study Evidence Comparator Efficacy
Katsumata et al. 2009 (JGOG 3016) Phase III TC, q3wk AUC 6/180 Seems to have superior OS

Chemotherapy

Supportive medications

  • "Standard premedication"

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

Regimen #4, q3wk AUC 6/175

Study Evidence Comparator Efficacy
Gordon et al. 2011 Phase III Carboplatin & Gemcitabine Seems not superior
Burger et al. 2011 (GOG 218) Phase III Carboplatin, Paclitaxel, Bevacizumab initiation Seems not superior
Carboplatin, Paclitaxel, Bevacizumab throughout Inferior PFS
Perren et al. 2011 (ICON7) Phase III Carboplatin, Paclitaxel, Bevacizumab Seems to have inferior PFS
Pignata et al. 2014 (MITO-7) Phase III TC, q1wk AUC 2/60 Seems not superior
du Bois et al. 2015 (AGO-OVAR 12) Phase III Carboplatin, Nintedanib, Paclitaxel Seems to have inferior PFS
Sugiyama et al. 2016 (JGOG3017/GCIG) Phase III Cisplatin & Irinotecan Seems not superior

Chemotherapy

21-day cycle for up to 6 cycles

Patients with complete response in Gordon et al. 2011 could optionally proceed to receive paclitaxel consolidation.

Regimen #5, q3wk AUC 6/180

Study Evidence Comparator Efficacy
Katsumata et al. 2009 (JGOG 3016) Phase III TC, dose-dense Seems to have inferior OS

Chemotherapy

Supportive medications

  • "Standard premedication"

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

Regimen #6, q3wk AUC 7.5/175

Study Evidence Comparator Efficacy
Ozols et al. 2003 (GOG 158) Phase III Cisplatin & Paclitaxel Seems to have non-inferior RFS

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
  3. 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. contains verified protocol link to PMC article PubMed
    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 contains verified protocol PubMed
  4. 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. link to original article contains verified protocol PubMed
    1. 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. link to original article PubMed
  5. 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 contains verified protocol PubMed
  6. 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 contains verified protocol PubMed
  7. 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. link to original article contains verified protocol PubMed
  8. 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; Multicentre Italian Trials in Ovarian cancer (MITO-7); Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens et du sein (GINECO); Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups (ENGOT-OV-10); Gynecologic Cancer InterGroup (GCIG) Investigators. 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. link to original article PubMed
  9. 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 contains verified protocol PubMed
  10. 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 PubMed
  11. 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. link to original article contains protocol PubMed

Carboplatin, Paclitaxel, Bevacizumab

back to top

Regimen #1, standard-dose bevacizumab

Study Evidence Comparator Efficacy
Burger et al. 2011 (GOG 218) Phase III Carboplatin & Paclitaxel Superior PFS

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

Regimen #2, low-dose bevacizumab

Study Evidence Comparator Efficacy
Perren et al. 2011 (ICON7) Phase III Carboplatin & Paclitaxel Seems to have superior PFS

Chemotherapy

  • 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 (Avastin) as follows:
    • Cycle 1: not given if chemotherapy starts within 4 weeks of surgery. If greater than 4 weeks after surgery: 7.5 mg/kg IV once on day 1
    • Cycles 2 to 6: 7.5 mg/kg IV once on day 1

21-day cycle for 6 cycles

Subsequent treatment

References

  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. link to original article contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed
  3. 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 PubMed

Cisplatin & Paclitaxel

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Regimen

Study Evidence Comparator Efficacy
Ozols et al. 2003 (GOG 158) Phase III Carboplatin & Paclitaxel Seems to have non-inferior RFS
Armstrong et al. 2006 Phase III Intraperitoneal Cisplatin & Paclitaxel Seems to have inferior OS
Walker et al. 2006 Phase III Intraperitoneal Cisplatin & Paclitaxel Not reported

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
  3. 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 contains verified protocol PubMed

Intraperitoneal therapy

Cisplatin & Paclitaxel

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Regimen

Study Evidence Comparator Efficacy
Armstrong et al. 2006 Phase III Cisplatin & Paclitaxel Seems to have superior OS
Walker et al. 2006 Phase III Cisplatin & Paclitaxel Not reported

Chemotherapy

  • Cisplatin (Platinol) 100 mg/m2 intraperitoneal 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 once on day 1, then 60 mg/m2 intraperitoneal rapid infusion once on day 8

Supportive medications

  • (Varies per reference)
  • "Standard premedication" for Paclitaxel (Taxol)
  • "Hydration and antiemetic agents" before Cisplatin (Platinol)
  • 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 (Taxol)
  • Supportive medications left to investigator discretion

21-day cycle for 6 cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed

Maintenance after first-line therapy

Altretamine monotherapy

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Regimen

Study Evidence
Rothenberg et al. 2001 (SWOG-9326) Phase II

Chemotherapy

28-day cycles for 6 months

References

  1. 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 contains protocol 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. PubMed

Bevacizumab monotherapy

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Regimen

Study Evidence
Burger et al. 2011 (GOG 218) Non-randomized portion of RCT
Perren et al. 2011 (ICON7) Non-randomized portion of RCT

Preceding treatment

Chemotherapy

21-day cycle for 12 cycles (ICON7) or up to 16 cycles (GOG 218)

References

  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. link to original article contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed

Paclitaxel monotherapy

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Regimen #1, 135 mg/m2 q4wk

Study Evidence
Gordon et al. 2011 Non-randomized portion of RCT

Preceding treatment

Chemotherapy

28-day cycle for up to 12 cycles

Regimen #2, 175 mg/m2 q3wk x 3

Study Evidence
Micha et al. 2005 Phase II, <20 patients in this subgroup

Preceding treatment

  • Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

21-day cycle for 3 cycles

Regimen #3, 175 mg/m2 q3wk x 12

Study Evidence
Micha et al. 2005 Phase II, <20 patients in this subgroup

Preceding treatment

  • Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

21-day cycle for 12 cycles

Regimen #4, 175 mg/m2 q4wk x 3

Study Evidence Comparator Efficacy
Markman et al. 2003 (GOG 178) Phase III Paclitaxel for 12 cycles Inferior PFS

Chemotherapy

28-day cycle for 3 cycles

Regimen #5, 175 mg/m2 q4wk x 12

Study Evidence Comparator Efficacy
Markman et al. 2003 (GOG 178) Phase III Paclitaxel for 3 cycles Superior PFS

Chemotherapy

28-day cycle for 12 cycles

References

  1. 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. link to original article contains verified protocol PubMed
    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 contains verified protocol link to PMC article PubMed
  2. 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 contains verified protocol PubMed
  3. 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 contains verified protocol PubMed
  4. 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 contains verified protocol PubMed

Pazopanib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Du Bois et al. 2014 (AGO-OVAR16) Phase III Placebo Superior PFS

Patients enrolled in 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.

Chemotherapy

24-month course

References

  1. 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 contains verified protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Du Bois et al. 2014 (AGO-OVAR16) Phase III Pazopanib Inferior PFS

No active antineoplastic treatment after at least 5 cycles of initial platinum-taxane treatment. Used as a comparator arm and here for reference purposes only.

References

  1. 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 contains verified protocol PubMed

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

Carboplatin monotherapy

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Regimen

Study Evidence Comparator Efficacy
Parmar et al. 2003 (ICON4/AGO-OVAR-2.2) Phase III Carboplatin & Paclitaxel
Cisplatin & Paclitaxel 		Seems to have inferior OS
Pfisterer et al. 2006 Phase III Carboplatin & Gemcitabine Inferior PFS

Chemotherapy

21-day cycle for 6 to 10 cycles

References

  1. 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. link to original article contains verified protocol PubMed
  2. 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 contains verified protocol PubMed

Carboplatin & Docetaxel

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

Study Evidence
Kushner et al. 2007 Phase II

Note: BSA was capped at 2 m2.

Chemotherapy

Supportive medications

28-day cycle for 6 cycles

Regimen #2, AUC 5/75

Study Evidence
Strauss et al. 2007 Phase II

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed

Carboplatin & Doxorubicin liposomal

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

Regimen

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2010 (CALYPSO) Phase III Carboplatin & Paclitaxel Superior PFS
Sehouli et al. 2016 (HECTOR) Randomized Phase II Carboplatin & Topotecan Seems not superior

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

Chemotherapy

Supportive medications

28-day cycle for 6 or more cycles, depending on response and toxicity

References

  1. 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 contains verified protocol PubMed
    1. 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. Epub 2012 Jul 26. link to original article contains verified protocol link to PMC article PubMed
  2. 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. 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 contains verified protocol PubMed

Carboplatin & Gemcitabine

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GC: Gemcitabine & Carboplatin

Regimen #1, limited duration

Study Evidence Comparator Efficacy
Pfisterer et al. 2006 Phase III Carboplatin Superior PFS
Aghajanian et al. 2012 (OCEANS) Phase III Carboplatin, Gemcitabine, Bevacizumab Inferior PFS

Chemotherapy

21-day cycle for 6 to 10 cycles

Regimen #2, indefinite

Study Evidence Comparator Efficacy
Sehouli et al. 2016 (HECTOR) Randomized Phase II Carboplatin & Topotecan Seems not superior

Chemotherapy

21-day cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol link to PMC article PubMed
    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
  3. 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. 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 contains verified protocol PubMed

Carboplatin, Gemcitabine, Bevacizumab

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Regimen

Study Evidence Comparator Efficacy
Aghajanian et al. 2012 (OCEANS) Phase III See link See link

Chemotherapy

21-day cycle for 6 to 10 cycles, based on response

Subsequent treatment

References

  1. 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 contains verified protocol link to PMC article PubMed
    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

Carboplatin & Paclitaxel

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CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin

Regimen #1, AUC 5/175, limited duration

Study Evidence Comparator Efficacy
Coleman et al. 2017 (NRG/GOG-0213) Phase III Carboplatin, Paclitaxel, Bevacizumab Might have inferior OS

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

Regimen #2, AUC 5/175, indefinite

Study Evidence Comparator Efficacy
Parmar et al. 2003 (ICON4/AGO-OVAR-2.2) Phase III Carboplatin Seems to have superior OS
Pujade-Lauraine et al. 2010 (CALYPSO) Phase III Carboplatin & PLD Inferior PFS
Oza et al. 2014 Randomized Phase II Carboplatin, Paclitaxel, Olaparib Inferior PFS
Sehouli et al. 2016 (HECTOR) Randomized Phase II Carboplatin & Topotecan Seems not superior
Coleman et al. 2017 (NRG/GOG-0213) Phase III Carboplatin, Paclitaxel, Bevacizumab Might have inferior OS

Chemotherapy

Supportive medications

21-day cycles

Regimen #3, AUC 6/175

Study Evidence Comparator Efficacy
Oza et al. 2014 Randomized Phase II Carboplatin, Paclitaxel, Olaparib Inferior PFS

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
    1. 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. Epub 2012 Jul 26. link to original article contains verified protocol link to PMC article PubMed
  3. 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 contains protocol PubMed
  4. 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. 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 contains verified protocol PubMed
  5. 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 contains protocol PubMed

Carboplatin, Paclitaxel, Olaparib

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Regimen

Study Evidence Comparator Efficacy
Oza et al. 2014 Randomized Phase II Carboplatin & Paclitaxel Superior PFS

Chemotherapy

21-day cycles

Total number of cycles is not specified in the abstract, but at completion of this portion, patients proceed to olaparib maintenance.

References

  1. 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 contains protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study Evidence
Rose et al. 2003 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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 contains verified protocol PubMed

Cisplatin & Paclitaxel

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Regimen

Study Evidence Comparator Efficacy
Parmar et al. 2003 (ICON4/AGO-OVAR-2.2) Phase III Carboplatin Seems to have superior OS

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed

Etoposide monotherapy

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Regimen

Study Evidence ORR
Rose et al. 1998 Phase II 34%

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21
    • Dosage for patients with previous pelvic radiation: 30 mg/m2 PO once per day on days 1 to 21; dose could be increased up to 50 mg/m2 depending on toxicity

28-day cycles

References

  1. 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. link to original article contains verified protocol PubMed

Paclitaxel, nanoparticle albumin-bound monotherapy

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Regimen

Study Evidence
Teneriello et al. 2009 Phase II

Chemotherapy

21-day cycle for 6 to 8 cycles

References

  1. 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 contains verified protocol PubMed

Rucaparib monotherapy

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Regimen

Study Evidence
Swisher et al. 2016 (ARIEL2 Part 1) Phase II

Chemotherapy

28-day cycles, given until progession of disease

References

  1. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article contains verified protocol PubMed

Maintenance after second-line therapy for platinum-sensitive disease

Bevacizumab monotherapy

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Regimen

Study Evidence Comparator Efficacy
Aghajanian et al. 2012 (OCEANS) Phase III See link See link

Preceding treatment

Chemotherapy

21-day cycles

References

  1. 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 contains verified protocol link to PMC article PubMed
    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

Niraparib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Mirza et al. 2016 (NOVA) Phase III Placebo Superior PFS

Preceding treatment

  • Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.

Chemotherapy

Continued until progression

References

  1. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. link to original article contains verified protocol PubMed

Olaparib monotherapy

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Regimen #1, 300 BID

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2017 (SOLO2/ENGOT-Ov21) Phase III Placebo Superior PFS

Patients had platinum-sensitive relapsed disease and BRCA1/2 mutations.

Chemotherapy

Continued until progression

Regimen #2, 400 BID

Study Evidence Comparator Efficacy
Ledermann et al. 2012 (D0810C00019) Randomized Phase II Placebo Seems to have superior OS (*)
Oza et al. 2014 Non-randomized portion of RCT

Reported efficacy for D0810C00019 based on the 2016 update.

Preceding treatment

Chemotherapy

Continued until progression

References

  1. Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. link to original article contains verified protocol PubMed
    1. Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article PubMed
  2. 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 contains protocol PubMed
  3. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article contains protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Ledermann et al. 2012 (D0810C00019) Randomized Phase II Olaparib Seems to have inferior OS (*)
Mirza et al. 2016 (NOVA) Phase III Niraparib Inferior PFS
Pujade-Lauraine et al. 2017 (SOLO2/ENGOT-Ov21) Phase III Olaparib Inferior PFS
Coleman et al. 2017 (ARIEL3) Phase III Rucaparib Inferior PFS

No active antineoplastic treatment after platinum-containing chemotherapy. Reported efficacy for D0810C00019 based on the 2016 update.

References

  1. Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. link to original article contains verified protocol PubMed
    1. Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article PubMed
  2. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. link to original article contains verified protocol PubMed
  3. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article contains protocol PubMed
  4. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Sep 12. [Epub ahead of print] link to original article PubMed

Rucaparib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Coleman et al. 2017 (ARIEL3) Phase III Placebo Superior PFS

Preceding treatment

Chemotherapy

28-day cycles, given until progession of disease

References

  1. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Sep 12. [Epub ahead of print] link to original article contains verified protocol PubMed

Relapsed or recurrent disease, platinum-resistant

Bevacizumab monotherapy

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Regimen

Study Evidence
Burger et al. 2007 Phase II
Cannistra et al. 2007 Phase II

Chemotherapy

21-day cycles

References

  1. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed

Docetaxel monotherapy

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Regimen

Study Evidence
Rose et al. 2003 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed

Doxorubicin liposomal monotherapy

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Regimen #1, 40 mg/m2

Study Evidence Comparator Efficacy
Ferrandina et al. 2008 Phase III Gemcitabine Might have inferior ORR
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Pegylated liposomal doxorubicin & Bevacizumab Inferior PFS
Lindemann et al. 2017 (Ovaresist) Phase III Tamoxifen Superior PFS

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.

Chemotherapy

Supportive medications

28-day cycles

Regimen #2, 50 mg/m2

Study Evidence Comparator Efficacy
Gordon et al. 2001 Phase III Topotecan Might have superior PFS
Mutch et al. 2007 Phase III Gemcitabine Seems not superior
Marth et al. 2016 (ENGOT-ov-6/TRINOVA-2) Phase III PLD & Trebananib Seems not superior

Chemotherapy

28-day cycles

References

  1. 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 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed content property of HemOnc.org
  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 contains verified protocol PubMed
  4. 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. link to original article contains verified protocol PubMed
    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. 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
  5. 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 contains protocol PubMed
  6. 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 contains protocol PubMed

Doxorubicin liposomal & Bevacizumab

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Regimen

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Pegylated liposomal doxorubicin Superior PFS

Chemotherapy

28-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    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. 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

Doxorubicin liposomal & Gemcitabine

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Regimen

Study Evidence
Ferrandina et al. 2005 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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 contains verified protocol PubMed

Etoposide monotherapy

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Regimen

Study Evidence ORR
Rose et al. 1998 Phase II 27%

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21
    • Dosage for patients with previous pelvic radiation: 30 mg/m2 PO once per day on days 1 to 21; dose could be increased up to 50 mg/m2 depending on toxicity

28-day cycles

References

  1. 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. link to original article contains verified protocol PubMed

Gemcitabine monotherapy

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Regimen #1, 2 weeks out of 3

Study Evidence Comparator Efficacy
Mutch et al. 2007 Phase III Pegylated liposomal doxorubicin Seems not superior
Kurzeder et al. 2016 (PENELOPE) Phase III Gemcitabine & Pertuzumab Seems not superior

Chemotherapy

21-day cycles

Regimen #2, 3 weeks out of 4

Study Evidence Comparator Efficacy
Ferrandina et al. 2008 Phase III Pegylated liposomal doxorubicin Might have superior ORR

Chemotherapy

28-day cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
  3. 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 contains verified protocol PubMed

Olaparib monotherapy

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Regimen

Study Evidence
Audeh et al. 2010 Phase II
Gelmon et al. 2011 Phase II
Kaufman et al. 2014 Phase II

Patients in Kaufman et al. 2014 were resistant to prior platinum-containing therapy.

Chemotherapy

Continued until progression

References

  1. 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. link to original article contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed
  3. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed

Paclitaxel monotherapy

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Regimen

Study Evidence Comparator Efficacy
Gynecologic Oncology Group et al. 2006 Phase II
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Paclitaxel & Bevacizumab Inferior PFS
Monk et al. 2014 (TRINOVA-1) Phase III Paclitaxel & Trebananib Inferior PFS
Pignata et al. 2015 (MITO 11) Randomized Phase II Paclitaxel & Pazopanib Inferior PFS
Kurzeder et al. 2016 (PENELOPE) Phase III Paclitaxel & Pertuzumab Seems not superior
Lindemann et al. 2017 (Ovaresist) Phase III Tamoxifen Superior PFS

Note: PENELOPE reports giving paclitaxel on days 1, 8, 15 of a 21-day cycle, which is identical to the schedule below. 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.

Chemotherapy

Supportive medications

28-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed
    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. 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
  3. 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
    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
  4. 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 11 investigators. 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 contains protocol PubMed
  5. 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 contains verified protocol PubMed
  6. 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 contains protocol PubMed

Paclitaxel & Bevacizumab

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Regimen

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Paclitaxel Superior PFS

Chemotherapy

28-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    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. 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

Paclitaxel & Pazopanib

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Regimen

Study Evidence Comparator Efficacy
Pignata et al. 2015 (MITO 11) Randomized Phase II Paclitaxel Superior PFS

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. 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 11 investigators. 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 contains protocol PubMed

Pazopanib monotherapy

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Regimen

Study Evidence
Friedlander et al. 2010 Phase II

Chemotherapy

given until progression of disease or unacceptable toxicity

References

  1. 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 contains verified protocol PubMed

Pemetrexed monotherapy

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Regimen

Study Evidence
Miller et al. 2009 Phase II

Chemotherapy

  • Pemetrexed (Alimta) 900 mg/m2 IV over 10 minutes once on day 1
    • Dosage for patients with previous radiation therapy: 700 mg/m2 IV over 10 minutes once on day 1

Supportive medications

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

21-day cycles

References

  1. 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. link to original article contains verified protocol link to PMC article PubMed

Topotecan monotherapy

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

Study Evidence Comparator Efficacy
Sehouli et al. 2011 Randomized Phase II 5-day topotecan Seems not superior
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Bevacizumab & Topotecan Inferior PFS

Chemotherapy

28-day cycle for up to 12 months; in AURELIA, topotecan was given until progression of disease or unacceptable toxicity

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

Study Evidence Comparator Efficacy
Sehouli et al. 2011 Randomized Phase II Weekly topotecan Seems not superior
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Bevacizumab & Topotecan Inferior PFS
Kurzeder et al. 2016 (PENELOPE) Phase III Topotecan & Pertuzumab Seems not superior

Chemotherapy

21-day cycle for up to 12 months (Sehouli et al. 2011) or until progression of disease or unacceptable toxicity

Regimen #3, 7.5 mg/m2, split dosing, q3wk

Study Evidence Comparator Efficacy
Gordon et al. 2001 Phase III Pegylated liposomal doxorubicin Might have inferior PFS

Chemotherapy

21-day cycles

References

  1. 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 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 contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed
  3. 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. link to original article contains verified protocol PubMed
    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. 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
  4. 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 contains verified protocol PubMed

Topotecan & Bevacizumab

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Regimen #1, topotecan 3 weeks out of 4

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Topotecan Superior PFS

Chemotherapy

28-day cycles

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

Study Evidence Comparator Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III Topotecan Superior PFS

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    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. 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

Vinorelbine monotherapy

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Regimen

Study Evidence
Rothenberg et al. 2004 Phase II

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains protocol PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

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