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	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!

49 regimens on this page 65 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: Chuang et al. Management and Care of Patients With Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update PubMed
- 2016: Chuang et al. Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline PubMed

ESMO

2018: Marth et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2017: Marth et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Colombo et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Haie-Meder et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Haie-Meder et al. Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Haie-Meder et al. Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

NCCN

NCCN Guidelines - Cervical Cancer
- 2019: Koh et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2015: Koh et al. Cervical Cancer, Version 2.2015 PubMed
- 2013: Koh et al. Cervical cancer. PubMed
- 2010: Greer et al. Cervical cancer. PubMed
- 2008: Greer et al. Cervical cancer. PubMed
- 2004: Teng et al. Cervical cancer guidelines. Clinical practice guidelines in oncology. PubMed

Neoadjuvant chemotherapy

Cisplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence
Park et al. 2004	2000-10 to 2002-01	Phase 2

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV over 2 hours once on day 1, given second
Paclitaxel (Taxol) 60 mg/m² IV over 3 hours once on day 1, given first

Supportive therapy

Dexamethasone (Decadron) 20 mg PO twice on day 1; 12 and 6 hours prior to paclitaxel
Cimetidine (Tagamet) 300 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
Antiemetics before and 3 days after chemotherapy

10-day cycle for 3 cycles

Subsequent treatment

Clinical response assessed after 3 cycles with pelvic examination and MRI. Treatment followed by surgery or radiation therapy.

References

Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. link to original article contains dosing details in manuscript PubMed

Definitive therapy for locally advanced disease

Brachytherapy protocol

Regimen

To be completed

Radiotherapy

Intracavitary brachytherapy with radium or its equivalent by the following study-specific criteria:
- Pearcey et al. 2002: See paper for details
- GOG 120, stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
  - Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy
- B9E-MC-JHQS & Sehouli et al. 2012: 30 to 3500 cGy delivered to point A
- GOG 219: 35 to 4360 cGy to point A
- GOG 120, stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
  - Patients that could not receive brachytherapy underwent additional external_beam_radiotherapy for a total dose of 6120 cGy
- GOG 123: 3000 cGy to point A for a total dose of 7500 cGy
- GOG 165: ONE of the following:
  - Low-dose rate intracavitary brachytherapy of 4000 cGy to point A given in 1 to 2 fractions
  - High-dose rate intracavitary brachytherapy of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
- GOG 165: Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete

References

GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078

Carboplatin & RT

Carboplatin & RT: Carboplatin & Radiation Therapy

Regimen variant #1, AUC-based carboplatin

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2023 (CALLA)	2019-02-15 to 2020-12-10	Phase 3 (C)	1a. Carboplatin, Durvalumab, RT 1b. Cisplatin, Durvalumab, RT	Did not meet primary endpoint of PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29

Radiotherapy

Concurrent radiation therapy, 180 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)

5-week course

Subsequent treatment

Brachytherapy

Regimen variant #2, BSA-based carboplatin

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Veerasarn et al. 2006	2001-2003	Phase 3 (C)	Carboplatin, UFT, RT	Did not meet co-primary endpoints of TTP/OS

Chemotherapy

Carboplatin (Paraplatin) 100 mg/m² IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, +/- 36

Radiotherapy

Concurrent radiation therapy

5- to 6-week course

References

Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P, Suntornpong N, Sangruchi S, Lertsanguansinchai P, Khorprasert C, Sookpreedee L, Udompunturak S. A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results. Gynecol Oncol. 2007 Jan;104(1):15-23. Epub 2006 Sep 25. link to original article contains dosing details in manuscript PubMed
CALLA: Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. link to original article contains dosing details in abstract PubMed NCT03830866

Cisplatin & RT

Cisplatin & RT: Cisplatin & Radiation Therapy

Regimen variant #1, weekly cisplatin x 5, no cap + 4500 cGy

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kenter et al. 2023 (EORTC-55994)	2002-05 to 2014-01	Phase 3 (C)	Neoadjuvant chemotherapy, then surgery	Did not meet primary endpoint of OS60
Monk et al. 2023 (CALLA)	2019-02-15 to 2020-12-10	Phase 3 (C)	1a. Carboplatin, Durvalumab, RT 1b. Cisplatin, Durvalumab, RT	Did not meet primary endpoint of PFS

Chemotherapy

Cisplatin (Platinol) 40 mg/m² IV once per day on days 1, 8, 15, 22, 29

Radiotherapy

Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 4500 cGy

5-week course

Subsequent treatment

Sequential brachytherapy (see paper for details)

Regimen variant #2, weekly cisplatin x 5, no cap + 5000 cGy

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lutgens et al. 2016 (RADCHOC)	2003-2009	Phase 3 (C)	RT-HT	Did not meet primary endpoint of EFS
Shrivastava et al. 2018 (CRACx)	2003-2011	Phase 3 (E-esc)	RT	Seems to have superior OS (secondary endpoint) OS60: 54% vs 46% (HR 0.82, 95% CI 0.68-0.98)

Chemotherapy

Cisplatin (Platinol) 40 mg/m² IV once per day on days 1, 8, 15, 22, 29

Supportive therapy

Ondansetron (Zofran) 16 mg (route not specified) once on day 1, prior to cisplatin
Dexamethasone (Decadron) 8 mg (route not specified) once on day 1, prior to cisplatin
Pre- and post- cisplatin hydration

Radiotherapy

Concurrent radiation therapy: 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 5000 cGy

5-week course

Subsequent treatment

Sequential brachytherapy (see paper for details)

Regimen variant #3, weekly cisplatin x 6, no cap

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pearcey et al. 2002	1991-1996	Phase 3 (E-esc)	RT	Did not meet primary endpoint of OS36
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (E-esc)	1. Cisplatin, Fluorouracil, Hydroxyurea, RT	Did not meet co-primary endpoints of PFS/OS
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (E-esc)	2. Hydroxyurea & RT	Superior OS (co-primary endpoint)
Dueñas-González et al. 2011 (B9E-MC-JHQS)	2002-2004	Phase 3 (C)	Cisplatin, Gemcitabine, RT	Seems to have inferior OS
Sehouli et al. 2012	2003-2008	Phase 3 (C)	Carboplatin & Paclitaxel, then RT	Did not meet primary endpoint of PFS
Zuliani et al. 2014	2003-2010	Phase 3 (E-esc)	RT	Superior OS¹ (co-primary endpoint) (HR 0.53, 95% CI 0.31-0.92)
DiSilvestro et al. 2014 (GOG 219)	2006-2009	Phase 3 (C)	Cisplatin, Tirapazamine, RT	Did not meet primary endpoint of PFS
Yang et al. 2022	2018-2020	Phase 3 (C)	Nedaplatin & RT	Inferior PFS
Lorusson et al. 2024 (KEYNOTE-A18)	2020-06-09 to 2022-12-15	Phase 3 (C)	Cisplatin, Pembrolizumab, RT	Inferior PFS

¹Reported efficacy is based on the 2020 update.
Note: In GOG 120, this regimen was intended for disease.

Chemotherapy

Cisplatin (Platinol) 40 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given 1 to 4 hours prior to radiation

Radiotherapy

Concurrent radiation therapy by the following study-specific criteria:
- GOG 120, stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
- GOG 219: 180 cGy x 23 to 25 fractions, for an initial dose of 41.4 to 4500 cGy
- Pearcey et al. 2002 & Zuliani et al. 2014: 180 cGy x 25 fractions, for an initial dose of 4500 cGy
- B9E-MC-JHQS & Sehouli et al. 2012: 180 cGy x 28 fractions, for an initial dose of 5040 cGy
- GOG 120, stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy
- Yang et al. 2022: 180 cGy/fraction/day, 5 days/week, a total of 25-28 fractions

6-week course, followed in 1 to 3 weeks by:

Subsequent treatment

Sequential brachytherapy

Regimen variant #4, weekly cisplatin x 6, capped

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Keys et al. 1999 (GOG 123)	1992-1997	Phase 3 (E-esc)	RT	Superior OS (co-primary endpoint) OS36: 83% vs 74% (RR 0.54, 95% CI 0.34-0.86)
Lanciano et al. 2005 (GOG 165)	1997-2000	Phase 3 (E-switch-ic)	Fluorouracil & RT	Might have superior ORR (secondary endpoint)

Chemotherapy

Cisplatin (Platinol) 40 mg/m² (maximum dose of 70 mg) IV once per day on days 1, 8, 15, 22, 29, 36, given 4 hours before radiation

Radiotherapy

Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 4500 cGy

6-week course, followed by:

Subsequent treatment

GOG 123: Sequential brachytherapy, then adjuvant hysterectomy
GOG 165: Sequential brachytherapy

Regimen variant #5, q3wk cisplatin x 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ryu et al. 2011 (KCCH GY 1005)	2002-2004	Phase 3 (E-switch-ic)	Cisplatin & RT; weekly cisplatin	Superior OS60 OS60: 89% vs 66.5% (HR 0.375, 95% CI 0.15-0.91)

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once per day on days 1, 22, 43

Radiotherapy

Concurrent radiation therapy: 1.8 to 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, (35 to 37)
- Total number of fractions: 25 to 28
- Total dose: 5000 cGy

9-week course

Subsequent treatment

Sequential brachytherapy (see paper for details)

References

GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
1. Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
GOG 123: Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. link to original article contains dosing details in manuscript PubMed
NCIC-CTG: Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. link to original article contains dosing details in manuscript PubMed
GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078
B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100
KCCH GY 1005: Ryu SY, Lee WM, Kim K, Park SI, Kim BJ, Kim MH, Choi SC, Cho CK, Nam BH, Lee ED. Randomized clinical trial of weekly vs triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e577-81. Epub 2011 Aug 11. link to original article contains dosing details in manuscript PubMed NCT01097252
Sehouli J, Runnebaum IB, Fotopoulou C, Blohmer U, Belau A, Leber H, Hanker LC, Hartmann W, Richter R, Keyver-Paik MD, Oberhoff C, Heinrich G, du Bois A, Olbrich C, Simon E, Friese K, Kimmig R, Boehmer D, Lichtenegger W, Kuemmel S; NOGGO; AGO. A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Ann Oncol. 2012 Sep;23(9):2259-64. Epub 2012 Feb 21. link to original article contains dosing details in manuscript PubMed
GOG 219: DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. Epub 2014 Jan 6. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00262821
Zuliani AC, Esteves SC, Teixeira LC, Teixeira JC, de Souza GA, Sarian LO. Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized controlled trial. J Clin Oncol. 2014 Feb 20;32(6):542-7. Epub 2014 Jan 21. link to original article PubMed
1. Update: Fachini AMD, Zuliani AC, Sarian LO, Teixeira JC, Esteves SCB, da Costa Machado H, Zeferino LC. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial. Gynecol Oncol. 2021 Feb;160(2):379-383. Epub 2020 Dec 16. link to original article PubMed
RADCHOC: Lutgens LC, Koper PC, Jobsen JJ, van der Steen-Banasik EM, Creutzberg CL, van den Berg HA, Ottevanger PB, van Rhoon GC, van Doorn HC, Houben R, van der Zee J. Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial. Radiother Oncol. 2016 Sep;120(3):378-382. Epub 2016 Feb 17. link to original article contains dosing details in abstract PubMed
CRACx: Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: a randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. link to original article contains dosing details in supplement link to PMC article PubMed NCT00193791
Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. link to original article link to PMC article contains dosing details in manuscript PubMed ChiCTR1800017108
EORTC-55994: Kenter GG, Greggi S, Vergote I, Katsaros D, Kobierski J, van Doorn H, Landoni F, van der Velden J, Reed N, Coens C, van Luijk I, Colombo N, Steen-Banasik EV, Ottevanger N, Casado A; EORTC-55994 Study Group. Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994. J Clin Oncol. 2023 Nov 10;41(32):5035-5043. Epub 2023 Sep 1. link to original article PubMed NCT00039338
CALLA: Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. link to original article contains dosing details in abstract PubMed NCT03830866
KEYNOTE-A18: Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. link to original article PubMed NCT04221945
NRG-GY006: NCT02466971

Cisplatin, Pembrolizumab, RT

Cisplatin, Pembrolizumab, RT: Cisplatin, Pembrolizumab, Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lorusson et al. 2024 (KEYNOTE-A18)	2020-06-09 to 2022-12-15	Phase 3 (E-RT-esc)	Cisplatin & RT	Superior PFS (co-primary endpoint) PFS24: 68% vs 57% (HR 0.70, 95% CI 0.55-0.89) Did not meet co-primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycles 1 & 2: 40 mg/m² IV once per day on days 1, 8, 15

Radiotherapy

Concurrent radiation therapy

Immunotherapy

Pembrolizumab (Keytruda) as follows:
- Cycles 1 to 5: 200 mg IV once on day 1
- Cycles 6 to 20: 400 mg IV once on day 1

21-day cycle for 5 cycles, then 42-day cycle for 15 cycles

References

KEYNOTE-A18: Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. link to original article PubMed NCT04221945

Cisplatin & Fluorouracil (CF) & RT

CF & RT: Cisplatin, Fluorouracil Radiation Therapy

Regimen variant #1, 70/4000 x 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Whitney et al. 1999 (GOG 85/SWOG 8695)	1986-1990	Phase 3 (E-esc)	Hydroxyurea & RT	Seems to have superior OS (co-primary endpoint) Median OS: NYR vs 59.8 mo (RR 0.74, 90% CI 0.58-0.95)
Peters et al. 2000 (GOG 109/SWOG-8797)	1991-1996	Phase 3 (E-esc)	Radiation therapy	Superior OS (co-primary endpoint) OS48: 81% vs 71% (HR 0.51)

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV over 2 hours once per day on days 1, 22, 43, 64
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, started on days 1, 22, 43, 64 (total dose: 16,000 mg/m²)

Radiotherapy

Concurrent radiation therapy 170 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 39 (29 fractions, for a total dose of 4930 cGy)
- Patients with positive high common iliac lymph nodes also received 150 cGy x 30 fractions, for a total dose of 4500 cGy

12-week course

Regimen variant #2, 75/4000 x 3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Morris et al. 1999 (RTOG 9001)	1990-1997	Phase 3 (E-esc)	Radiation therapy	Superior OS (primary endpoint) OS60: 73% vs 58%

Note: radiation could start one day before chemotherapy, on "day 0".

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 4 hours once per day on days 1, 22, 43, given first
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, started on days 1, 22, 43 (total dose: 12,000 mg/m²)

Radiotherapy

Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)

9-week course

Subsequent treatment

Brachytherapy (see paper for details)

References

RTOG 9001: Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. link to original article contains dosing details in manuscript PubMed
GOG 85/SWOG 8695: Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. link to original article PubMed
GOG 109/SWOG-8797: Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. link to original article contains dosing details in manuscript PubMed

Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT

Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, Radiation Therapy

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (E-esc)	1. Cisplatin & RT	Did not meet co-primary endpoints of PFS/OS
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (E-esc)	2. Hydroxyurea & RT	Superior OS (co-primary endpoint)

Definitive therapy

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 29
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose per cycle: 4000 mg/m²)
Hydroxyurea (Hydrea) 2000 mg/m² PO two times per week, given 2 hours before radiation on weeks 1 to 6

Radiotherapy

Concurrent radiation therapy by the following stage-based criteria:
- Stage IIB: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 25 (24 fractions, for an initial dose of 4080 cGy)
- Stage III or IVA: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (30 fractions, for an initial dose of 5100 cGy)

5- to 6-week course, followed by:

Consolidation

Radiotherapy

Stage IIB patients received 4000 cGy by intracavitary brachytherapy, for a total dose of 8080 cGy to point A
Stage III or IVA disease received 3000 cGy by intracavitary brachytherapy, for a total dose of 8100 cGy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy

One course

References

GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
1. Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed

Cisplatin & Gemcitabine (GC) & RT

Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dueñas-González et al. 2011 (B9E-MC-JHQS)	2002-2004	Phase 3 (E-esc)	Cisplatin & RT	Seems to have superior PFS (primary endpoint) PFS36: 74.4% vs 65% (HR 0.68, 95% CI 0.49-0.95) Seems to have superior OS (secondary endpoint) Median OS: NYR vs NYR (HR 0.68, 95% CI 0.49-0.95)
Cetina et al. 2013	2004-2009	Non-randomized part of phase 3 RCT

Chemotherapy

Cisplatin (Platinol) 40 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given first, 1 to 2 hours before radiation
Gemcitabine (Gemzar) 125 mg/m² IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given second, 1 to 2 hours before radiation

Radiotherapy

Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for an initial dose of 5040 cGy)

6-week course

Subsequent treatment

B9E-MC-JHQS: Brachytherapy (30 to 3500 cGy delivered to point A), then adjuvant GC, in 2 weeks
Cetina et al. 2013: Brachytherapy verus radical hysterectomy

References

B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100
Cetina L, González-Enciso A, Cantú D, Coronel J, Pérez-Montiel D, Hinojosa J, Serrano A, Rivera L, Poitevin A, Mota A, Trejo E, Montalvo G, Muñoz D, Robles-Flores J, de la Garza J, Chanona J, Jiménez-Lima R, Wegman T, Dueñas-González A. Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients. Ann Oncol. 2013 Aug;24(8):2043-7. Epub 2013 Apr 21. link to original article contains dosing details in abstract PubMed

Fluorouracil & RT

5-FU & RT: 5-FluouroUracil & Radiation Therapy

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lanciano et al. 2005 (GOG 165)	1997-2000	Phase 3 (E-switch-ic)	Cisplatin & RT	Might have inferior ORR (secondary endpoint)

Definitive therapy

Chemotherapy

Fluorouracil (5-FU) 225 mg/m²/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29, 36 (total dose: 6750 mg/m²)

Radiotherapy

Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for an initial dose of 4080 cGy)

6-week course, followed by:

Consolidation

Radiotherapy

- EITHER Low-dose rate intracavitary brachytherapy of 4000 cGy to point A given in 1 to 2 fractions
- OR High-dose rate intracavitary brachytherapy of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete

References

GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078

Hydroxyurea & RT

Hydroxyurea & RT: Hydroxyurea & Radiation Therapy

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hreshchyshyn et al. 1979 (GOG 04)	1970-1976	Phase 3 (E-esc)	Radiation therapy	Seems to have superior OS
Stehman et al. 1988 (GOG 56)	1981-06 to 1985-12	Randomized	Misonidazole & RT	Seems to have superior PFS¹
Whitney et al. 1999 (GOG 85/SWOG 8695)	1986-1990	Phase 3 (C)	Cisplatin, Fluorouracil, RT	Seems to have inferior OS
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (C)	1. Cisplatin & RT	Inferior OS
Rose et al. 1999 (GOG 120)	1992-1997	Phase 3 (C)	2. Cisplatin, Fluorouracil, Hydroxyurea, RT	Inferior OS

¹Reported efficacy for GOG 56 is based on the 1993 update.

Definitive therapy

Chemotherapy

Hydroxyurea (Hydrea) as follows:
- Weeks 1 to 6: 2000 mg/m² PO two times per week, given 2 hours before radiation

Radiotherapy

Concurrent radiation therapy by the following stage-based criteria:
- Stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
- Stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy

7- to 9-week course

Consolidation

Radiotherapy

Intracavitary brachytherapy by the following stage-based criteria:
- Stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
Stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy

References

Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA. Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys. 1979 Mar;5(3):317-22. link to original article PubMed
GOG 56: Stehman FB, Bundy BN, Keys H, Currie JL, Mortel R, Creasman WT. A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix: A preliminary report of a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1988 Jul;159(1):87-94. link to original article PubMed
1. Update: Stehman FB, Bundy BN, Thomas G, Keys HM, d'Ablaing G 3rd, Fowler WC Jr, Mortel R, Creasman WT. Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial. J Clin Oncol. 1993 Aug;11(8):1523-8. link to original article PubMed
GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
1. Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
GOG 85/SWOG 8695: Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. link to original article PubMed

Nedaplatin & RT

Nedaplatin & RT: Nedaplatin & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Yang et al. 2022	2018-2020	Phase 3 (E-switch-ic)	Cisplatin & RT	Superior PFS36 (primary endpoint) Median PFS: 30 vs 28 mo (HR 0.25, 95% CI 0.08-0.77)

Chemotherapy

Nedaplatin (Aqupla) 30 mg/m² IV once per day on days 1, 8, 15, 22, 29, +/- 36

Radiotherapy

Concurrent radiation therapy 180 cGy per day, 5 days/week, a total of 25-28 fractions

References

Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. link to original article link to PMC article contains dosing details in manuscript PubMed ChiCTR1800017108

Adjuvant therapy

Carboplatin & Ifosfamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Blohmer et al. 2011 (NOGGO-AGO)	1999-2001	Phase 3 (C)	See link	See link

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Preceding treatment

Wertheim-Meigs radical abdominal hysterectomy

Chemotherapy

Carboplatin (Paraplatin) AUC 4 IV over 60 minutes once on day 1
Ifosfamide (Ifex) 1600 mg/m² IV over 6 hours once per day on days 1 to 3, with mesa

Supportive therapy

Mesna (Mesnex) 1600 mg/m² IV over 6 hours once per day on days 1 to 3, with ifosfamide

21-day cycle for 4 cycles

Subsequent treatment

Pelvic EBRT x 5040 cGy

References

NOGGO-AGO: Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article contains dosing details in manuscript PubMed

Cisplatin & Gemcitabine (GC)

Regimen

Study	Dates of enrollment	Evidence
Dueñas-González et al. 2011 (B9E-MC-JHQS)	2002-2004	Non-randomized part of phase 3 RCT

Preceding treatment

Definitive Cisplatin, Gemcitabine, RT

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

21-day cycle for 2 cycles

References

B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100

Radiation therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Blohmer et al. 2011 (NOGGO-AGO)	1999-2001	Phase 3 (C)	See link	See link

Preceding treatment

Surgery, then adjuvant Carboplatin & Ifosfamide x 4

Radiotherapy

External beam radiotherapy: 180 cGy for 28 fractions, for a total dose of 5040 cGy
If resection margins positive, patients received one of the following:
- EBRT boost of 2 x 500 cGy
- Low-dose brachytherapy

6-week course

References

NOGGO-AGO: Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article contains dosing details in manuscript PubMed

Persistent, recurrent, or metastatic disease, first-line therapy

ABCP

ABCP: Atezolizumab, Bevacizumab, Carboplatin, Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oaknin et al. 2023 (BEATcc)	2018-10-08 to 2021-08-20	Phase 3 (E-esc)	1a. CP & Bevacizumab 1b. Cisplatin, Paclitaxel, Bevacizumab	Superior OS (co-primary endpoint) Median OS: 32.1 vs 22.8 mo (HR 0.68, 95% CI 0.52-0.88) Superior PFS (co-primary endpoint) Median PFS: 13.7 vs 10.4 mo (HR 0.62, 95% CI 0.49-0.78)

Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.

Chemotherapy

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

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

Targeted therapy

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

21-day cycles

References

BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839

Carboplatin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Weiss et al. 1990	NR	Phase 2

Chemotherapy

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

28-day cycles

References

Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS; SWOG. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. link to original article contains dosing details in abstract PubMed

Carboplatin & Docetaxel

Regimen variant #1, 6 cycles

Study	Dates of enrollment	Evidence
Takekida et al. 2010	2004-01 to 2005-12	Phase 2

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
Docetaxel (Taxotere) 60 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Dexamethasone (Decadron)
Ondansetron (Zofran) or Granisetron
Filgrastim (Neupogen) 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia

21-day cycle for up to 6 cycles

Regimen variant #2, indefinite

Study	Dates of enrollment	Evidence
Nagao et al. 2005	2001-2004	Pilot, fewer than 20 pts

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
Docetaxel (Taxotere) 60 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Dexamethasone (Decadron)
Ondansetron (Zofran) or Granisetron
Filgrastim (Neupogen) 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia

21-day cycles

References

Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer: a pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. link to original article contains dosing details in manuscript PubMed
Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. link to original article PubMed

Carboplatin & Paclitaxel (CP)

TC: Taxol (Paclitaxel) & Carboplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pectasides et al. 2009a	NR	Phase 2
Kitagawa et al. 2015 (JCOG0505)	2006-2009	Phase 3 (E-switch-ic)	Cisplatin & Paclitaxel	Non-inferior OS (primary endpoint) Median OS: 17.5 vs 18.3 mo (HR 0.994, 90% CI 0.79-1.25)
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (C)	1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab	Inferior OS

Note: Pectasides et al. 2009a allowed the regimen to be given up to 9 cycles. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

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

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

References

Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. link to original article contains dosing details in abstract PubMed
JCOG0505: Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00295789
KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Carboplatin & Paclitaxel (CP) & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (C)	1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab	Inferior OS
Oaknin et al. 2023 (BEATcc)	2018-10-08 to 2021-08-20	Phase 3 (C)	1a. ABCP 1b. Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab	Inferior PFS/OS

Note: In KEYNOTE-826, the decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m² IV once on day 1

Targeted therapy

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

21-day cycles

References

KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839

Carboplatin & Paclitaxel (CP), Bevacizumab, Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (E-RT-esc)	1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab	Superior OS¹ (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77)

¹Reported efficacy is based on the 2023 update for all patients.
Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m² IV once on day 1

Targeted therapy

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

Immunotherapy

Pembrolizumab (Keytruda) as follows:
- Cycles 1 up to 35: 200 mg IV once on day 1

21-day cycles

References

KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Carboplatin & Paclitaxel (CP) & Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (E-RT-esc)	1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab	Superior OS¹ (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77)

¹Reported efficacy is based on the 2023 update for all patients.
Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m² IV once on day 1

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Cisplatin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Thigpen et al. 1979a	NR in abstract	Phase 2
Bonomi et al. 1985 (GOG 43)	1978-1982	Phase 3 (C)	1. Cisplatin; higher dose 2. Cisplatin; higher dose, split doses	Did not meet primary endpoint of ORR
Thigpen et al. 1989 (GOG 64)	1982-1985	Phase 3 (C)	Cisplatin; CI	Did not meet primary efficacy endpoints
Omura et al. 1997 (GOG 110)	1990-1994	Phase 3 (C)	1. Cisplatin & Ifosfamide	Inferior PFS
Omura et al. 1997 (GOG 110)	1990-1994	Phase 3 (C)	2. Cisplatin & Mitolactol	Did not meet primary endpoint of ORR
Vermorken et al. 2001	1986-1991	Phase 3 (C)	BEMP	Did not meet primary endpoint of ORR
Moore et al. 2004 (GOG 169)	1997-1999	Phase 3 (C)	Cisplatin & Paclitaxel	Inferior PFS
Long et al. 2005 (GOG 179)	1999-2002	Phase 3 (C)	1. Cisplatin & Topotecan	Seems to have inferior OS
Long et al. 2005 (GOG 179)	1999-2002	Phase 3 (C)	2. MVAC	Not reported
Aoki et al. 2018 (Taiho 10020380)	2008-2011	Phase 3 (C)	Cisplatin & S-1	Did not meet primary endpoint of OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1

21-day cycles; if not responding, given for maximum of 6 cycles

References

Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J; Gynecologic Oncology Group. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1549-55. PubMed
GOG 43: Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. link to original article PubMed
GOG 64: Thigpen JT, Blessing JA, DiSaia PJ, Fowler WC Jr, Hatch KD. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1989 Feb;32(2):198-202. link to original article contains dosing details in abstract PubMed
GOG 110: Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. link to original article contains dosing details in abstract PubMed
Vermorken JB, Zanetta G, Freire de Oliveira C, van der Burg ME, Lacave AJ, Teodorovic I, Boes GH, Colombo N; EORTC Gynecological Cancer Cooperative Group. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol. 2001 Jul;12(7):967-74. link to original article PubMed
GOG 169: Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains dosing details in manuscript PubMed
GOG 179: Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains dosing details in manuscript PubMed NCT00003945
Taiho 10020380: Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, Katsumata N, Cha SD, Kim JH, Kim BG, Hirashima Y, Fujiwara K, Kim YT, Kim SM, Chung HH, Chang TC, Kamura T, Takizawa K, Takeuchi M, Kang SB. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer. 2018 Aug;119(5):530-537. Epub 2018 Aug 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00770874

Cisplatin & Gemcitabine (GC)

GC: Gemcitabine, Cisplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2009 (GOG 204)	2003-2007	Phase 3 (E-switch-ic)	1. Cisplatin & Paclitaxel	Seems to have inferior PFS (secondary endpoint)
			2. Cisplatin & Topotecan	Did not meet primary endpoint of OS
			3. Cisplatin & Vinorelbine	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

21-day cycles

References

GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077

Cisplatin & Ifosfamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Omura et al. 1997 (GOG 110)	1990-1994	Phase 3 (E-esc)	1. Cisplatin	Superior PFS (secondary endpoint)
Omura et al. 1997 (GOG 110)	1990-1994	Phase 3 (E-esc)	2. Cisplatin & Mitolactol	Not reported
Bloss et al. 2002 (GOG 149)	1994-1997	Phase 3 (C)	CIB	Did not meet primary endpoint of ORR

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 1 concurrent with mesna

Supportive therapy

Mesna (Mesnex) 6000 mg/m² IV continuous infusion over 36 hours, started on day 1 concurrent with ifosfamide

21-day cycle for up to 6 cycles

References

GOG 110: Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. link to original article contains dosing details in abstract PubMed
GOG 149: Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, Markman M, Benda J. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2002 Apr 1;20(7):1832-7. link to original article PubMed

Cisplatin & Mitomycin

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Wagenaar et al. 2001	NR	Phase 2	ORR: 42% (95% CI: 26-61%)

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1, given second
Mitomycin (Mutamycin) 6 mg/m² IV push once on day 1, given first

Supportive therapy

1 liter NS over 1 hour once on day 1, prior to chemotherapy, then 1 liter NS over 1 hour once on day 1, after cisplatin
Furosemide (Lasix) (route/dose not specified) once on day 1, prior to chemotherapy
Mannitol IV push once on day 1, prior to cisplatin

28-day cycle for 9 cycles

References

Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB; EORTC Gynecological Cancer Group. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix: a European Organisation for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. link to original article contains dosing details in manuscript PubMed

Cisplatin & Paclitaxel

PC: Paclitaxel & Cisplatin
CP: Cisplatin & Paclitaxel
TP: Taxol (Paclitaxel) & Platinol (Cisplatin)

Regimen variant #1, 50/135, 3 hr paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (C)	1. Cisplatin, Paclitaxel, Bevacizumab	Inferior OS¹
			2. Paclitaxel & Topotecan	Did not meet primary endpoint of OS
			3. Paclitaxel, Topotecan, Bevacizumab	Not reported

¹Reported efficacy is based on the 2017 update.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Paclitaxel (Taxol) 135 mg/m² IV once on day 1

21-day cycles until CR or indefinitely

Regimen variant #2, 50/135, CI paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Moore et al. 2004 (GOG 169)	1997-1999	Phase 3 (E-esc)	Cisplatin	Superior PFS (secondary endpoint) Superior ORR (primary endpoint)
Monk et al. 2009 (GOG 204)	2003-2007	Phase 3 (C)	1. Cisplatin & Gemcitabine	Seems to have superior PFS (secondary endpoint)
			2. Cisplatin & Topotecan	Did not meet primary endpoint of OS
			3. Cisplatin & Vinorelbine	Might have superior PFS (secondary endpoint)
Kitagawa et al. 2015 (JCOG0505)	2006-2009	Phase 3 (C)	Carboplatin & Paclitaxel	Non-inferior OS

Note: patients in JCOG0505 received a maximum of 6 cycles.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 2
Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive therapy

(varies depending on reference):
Dexamethasone (Decadron)
Diphenhydramine (Benadryl)
H2 receptor antagonist such as Cimetidine (Tagamet) or Ranitidine (Zantac)
Prophylactic antiemetics
"Adequate IV hydration and electrolyte replacement"

21-day cycles; if not responding, given for maximum of 6 cycles.

Regimen variant #3, 50/175

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (C)	1. Cisplatin, Paclitaxel, Bevacizumab	Inferior OS¹
			2. Paclitaxel & Topotecan	Did not meet primary endpoint of OS
			3. Paclitaxel, Topotecan, Bevacizumab	Not reported
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (C)	1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab	Inferior OS

¹Reported efficacy is based on the 2017 update.
Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

Chemotherapy

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

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

References

GOG 169: Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains dosing details in manuscript PubMed
GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
1. Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
2. Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed
JCOG0505: Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00295789
KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Cisplatin, Paclitaxel, Bevacizumab

CP+Bev: Cisplatin, Paclitaxel, Bevacizumab

ESMO-preferred (I-A, 2017)

Regimen variant #1, 135 mg/m² paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (E-RT-esc)	1. Cisplatin & Paclitaxel	Superior OS¹ (primary endpoint) Median OS: 16.8 vs 13.3 mo (HR 0.77, 95% CI 0.62-0.95)
			2. Paclitaxel & Topotecan	Did not meet primary endpoint of OS¹
			3. Paclitaxel, Topotecan, Bevacizumab	Not reported

¹Reported efficacy is based on the 2017 update.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Paclitaxel (Taxol) 135 mg/m² IV once on day 1

Targeted therapy

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

21-day cycles until CR or indefinitely

Regimen variant #2, 175 mg/m² paclitaxel

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (E-RT-esc)	1. Cisplatin & Paclitaxel	Superior OS¹ (primary endpoint) Median OS: 16.8 vs 13.3 mo (HR 0.77, 95% CI 0.62-0.95)
			2. Paclitaxel & Topotecan	Did not meet primary endpoint of OS¹
			3. Paclitaxel, Topotecan, Bevacizumab	Not reported
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (C)	1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab	Inferior OS
Oaknin et al. 2023 (BEATcc)	2018-10-08 to 2021-08-20	Phase 3 (C)	1a. ABCP 1b. Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab	Inferior PFS/OS

¹Reported efficacy for this comparison in GOG 240 is based on the 2017 update.
Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. The decision to give bevacizumab in KEYNOTE-826 was at the discretion of the treating institution and was not a randomization.

Chemotherapy

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

Targeted therapy

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

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

References

GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
1. Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
2. Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed
KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839

Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oaknin et al. 2023 (BEATcc)	2018-10-08 to 2021-08-20	Phase 3 (E-esc)	1a. CP & Bevacizumab 1b. Cisplatin, Paclitaxel, Bevacizumab	Superior OS (co-primary endpoint) Median OS: 32.1 vs 22.8 mo (HR 0.68, 95% CI 0.52-0.88) Superior PFS (co-primary endpoint) Median PFS: 13.7 vs 10.4 mo (HR 0.62, 95% CI 0.49-0.78)

Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.

Chemotherapy

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

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

Targeted therapy

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

21-day cycles

References

BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839

Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (E-RT-esc)	1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab	Superior OS¹ (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77)

¹Reported efficacy is based on the 2023 update for all patients.
Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycles 1 to 6 (see note): 50 mg/m² IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m² IV once on day 1

Targeted therapy

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

Immunotherapy

Pembrolizumab (Keytruda) as follows:
- Cycles 1 up to 35: 200 mg IV once on day 1

21-day cycles

References

KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Cisplatin, Paclitaxel, Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Colombo et al. 2021 (KEYNOTE-826)	2018-2020	Phase 3 (E-RT-esc)	1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab	Superior OS¹ (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77)

¹Reported efficacy is based on the 2023 update for all patients.
Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycles 1 to 6 (see note): 50 mg/m² IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m² IV once on day 1

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
1. HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
2. Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed

Cisplatin & Topotecan

TC: Topotecan & Cisplatin
CT: Cisplatin & Topotecan

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Long et al. 2005 (GOG 179)	1999-2002	Phase 3 (E-RT-esc)	1. Cisplatin	Seems to have superior OS (primary endpoint) Median OS: 9.4 vs 6.5 mo (RR 0.76, 95% CI 0.59-0.98)
Long et al. 2005 (GOG 179)	1999-2002	Phase 3 (E-RT-esc)	2. MVAC	Not reported
Monk et al. 2009 (GOG 204)	2003-2007	Phase 3 (E-switch-ic)	1. Cisplatin & Gemcitabine	Did not meet primary endpoint of OS
			2. Cisplatin & Paclitaxel	Did not meet primary endpoint of OS
			3. Cisplatin & Vinorelbine	Did not meet primary endpoint of OS
Coronel et al. 2010 (006/027/ICI)	2007-2009	Phase 3 (C)	CT + HV	Seems to have inferior PFS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1, given second
Topotecan (Hycamtin) 0.75 mg/m² IV over 30 minutes once per day on days 1 to 3, given first

21-day cycle for up to 6 cycles

References

GOG 179: Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains dosing details in manuscript PubMed NCT00003945
GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
006/027/ICI: Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M, Vidal S, Dueñas-González A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer: preliminary results. Med Oncol. 2011 Dec;28 Suppl 1:S540-6. Epub 2010 Oct 8. link to original article contains dosing details in manuscript PubMed NCT00532818

Cisplatin & Vinorelbine (CVb)

CVb: Cisplatin & Vinorelbine
VC: Vinorelbine, Cisplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Monk et al. 2009 (GOG 204)	2003-2007	Phase 3 (E-switch-ic)	1. Cisplatin & Gemcitabine	Did not meet primary endpoint of OS
			2. Cisplatin & Paclitaxel	Might have inferior PFS (primary endpoint)
			3. Cisplatin & Topotecan	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1 & 8

21-day cycles; if not responding, given for maximum of 6 cycles

References

GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077

Ifosfamide monotherapy

Regimen

Study	Dates of enrollment	Evidence
Coleman et al. 1986	NR	Phase 2
Sutton et al. 1993b	1985-07 to 1990-12	Phase 2
Sutton et al. 1993a	1988-01 to 1990-02	Phase 2

Chemotherapy

Ifosfamide (Ifex) by the following exposure-based criteria:
No previous pelvic radiation or other chemotherapy: 1500 mg/m² IV once per day on days 1 to 5
Previous pelvic radiation or other chemotherapy: 1200 mg/m² IV once per day on days 1 to 5

Supportive therapy

Mesna (Mesnex) at 20% of ifosfamide dose (for example, 300 mg/m² for 1500 mg/m² dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5

21-day cycles

Dose and schedule modifications

Ifosfamide (Ifex) dose could be increased by 300 mg/m² or decreased by 20% depending on toxicity

References

Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, Wiltshaw E. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. link to original article PubMed
Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY; Gynecologic Oncology Group. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. link to original article PubMed
Sutton GP, Blessing JA, DiSaia PJ, McGuire WP; Gynecologic Oncology Group. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. link to original article contains dosing details in manuscript PubMed

Paclitaxel monotherapy

Regimen variant #1, 135 mg/m²

Study	Dates of enrollment	Evidence
McGuire et al. 1996	1990	Phase 2
Curtin et al. 2001	1994	Phase 2

Note: this was the dosage used for patients with previous pelvic radiation.

Chemotherapy

Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive therapy

Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycles

Dose and schedule modifications

Paclitaxel (Taxol) dose could be changed to 110 or 200 mg/m² depending on toxicity

Regimen variant #2, 170 mg/m²

Study	Dates of enrollment	Evidence
McGuire et al. 1996	1990	Phase 2
Curtin et al. 2001	1994	Phase 2

Chemotherapy

Paclitaxel (Taxol) by the following exposure-based criteria:
- No previous pelvic radiation: 170 mg/m² IV continuous infusion over 24 hours, started on day 1
- Previous pelvic radiation: 135 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive therapy

Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycles

Dose and schedule modifications

Paclitaxel (Taxol) dose could be changed to 110 or 200 mg/m² depending on toxicity

Regimen variant #3, 250 mg/m²

Study	Dates of enrollment	Evidence
Kudelka et al. 1996	NR	Phase 2

Chemotherapy

Paclitaxel (Taxol) 250 mg/m² IV over 3 hours once on day 1

Supportive therapy

Dexamethasone (Decadron) 20 mg PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to paclitaxel
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 2, 24 hours after paclitaxel, given until day 19 or until ANC greater or equal to 10,000/μL

21-day cycles

Dose and schedule modifications

Paclitaxel (Taxol) dose could be changed to 275, 225, or 200 mg/m² depending on toxicity

References

McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G; Gynecologic Oncology Group. Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. link to original article contains dosing details in manuscript PubMed
Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
1. Update: Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. link to original article PubMed
Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD; Gynecologic Oncology Group. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. link to original article contains dosing details in manuscript PubMed

Paclitaxel & Topotecan

TP: Topotecan, Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (C)	1. Cisplatin & Paclitaxel	Did not meet primary endpoint of OS
			2. Cisplatin, Paclitaxel, Bevacizumab	Not reported
			3. Paclitaxel, Topotecan, Bevacizumab	Did not meet primary endpoint of OS¹

¹Reported efficacy is based on the 2017 update.
Note: per the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV once on day 1
Topotecan (Hycamtin) 0.75 mg/m² IV once per day on days 1 to 3

21-day cycles

References

GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
1. Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
2. Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed

Paclitaxel, Topotecan, Bevacizumab

TP+Bev: Topotecan, Paclitaxel, Bevacizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2014 (GOG 240)	2009-2012	Phase 3 (E-RT-esc)	1. Cisplatin & Paclitaxel	Not reported
			2. Cisplatin, Paclitaxel, Bevacizumab	Not reported
			3. Paclitaxel & Topotecan	Did not meet primary endpoint of OS¹

¹Reported efficacy is based on the 2017 update.
Note: in the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV once on day 1
Topotecan (Hycamtin) 0.75 mg/m² IV once per day on days 1 to 3

Targeted therapy

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

21-day cycles

References

GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
1. Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
2. Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed

Topotecan monotherapy

Regimen variant #1, q3wk

Study	Dates of enrollment	Evidence
Bookman et al. 2000 (GOG 127-F)	1994-12 to NR	Phase 2

Chemotherapy

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

21-day cycles

Regimen variant #2, q4wk

Study	Dates of enrollment	Evidence
Muderspach et al. 2001 (GOG 76-U)	1994-01 to 1995-12	Phase 2

Chemotherapy

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

28-day cycles

References

Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA; Gynecologic Oncology Group. Topotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. link to original article contains dosing details in manuscript PubMed
GOG 76-U: Muderspach LI, Blessing JA, Levenback C, Moore JL Jr; Gynecologic Oncology Group. A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Gxroup study. Gynecol Oncol. 2001 May;81(2):213-5. link to original article contains dosing details in manuscript PubMed

Vinorelbine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Morris et al. 1998	1993-1995	Phase 2	ORR: 18%

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once on day 1

7-day cycles

References

Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. link to original article contains dosing details in manuscript PubMed

Advanced or metastatic disease, subsequent lines of therapy

Bevacizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Monk et al. 2009 (GOG 227-C)	2002-2006	Phase 2

Targeted therapy

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

21-day cycles

References

Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD; Gynecologic Oncology Group. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. link to original article contains dosing details in manuscript link to PMC article PubMed

Cemiplimab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (E-switch-ooc)	1a. Pemetrexed 1b. Topotecan 1c. Irinotecan 1d. Gemcitabine 1e. Vinorelbine	Superior OS (primary endpoint) Median OS: 12 vs 8.5 mo (HR 0.69, 95% CI 0.56-0.84)

Immunotherapy

Cemiplimab (Libtayo) 350 mg IV once on day 1

21-day cycle for up to 32 cycles (96 weeks)

References

EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267

Cisplatin & Gemcitabine (GC)

GC: Gemcitabine, Cisplatin

Regimen

Study	Dates of enrollment	Evidence
Brewer et al. 2006	2001-2002	Phase 2

Chemotherapy

Cisplatin (Platinol) 30 mg/m² IV once on day 1, given first
Gemcitabine (Gemzar) 800 mg/m² IV once per day on days 1 & 8, given second

28-day cycles

References

Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL; Gynecologic Oncology Group. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. link to original article contains dosing details in manuscript PubMed

Docetaxel monotherapy

Regimen variant #1, 36 mg/m², 3 weeks out of 4

Study	Dates of enrollment	Evidence
Garcia et al. 2008	2004-07 to 2005-04	Phase 2

Chemotherapy

Docetaxel (Taxotere) 36 mg/m² IV over 60 minutes once per day on days 1, 8, 15

Supportive therapy

Dexamethasone (Decadron) 8 mg PO the evening before, morning of, and evening of each dose of docetaxel

28-day cycles

Regimen variant #2, 100 mg/m², q3wk

Study	Dates of enrollment	Evidence
Garcia et al. 2007	2002-06 to 2004-12	Phase 2

Chemotherapy

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

21-day cycles

References

Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 2007 Aug;30(4):428-31. link to original article contains dosing details in abstract PubMed
Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. link to original article contains dosing details in manuscript PubMed

FULV

FULV: 5-FU & LeucoVorin

Regimen variant #1, 1850/200

Study	Dates of enrollment	Evidence
Look et al. 1996	1990-1992	Phase 2
Look et al. 1997	1993-1995	Phase 2

Note: it is not entirely clear from these publications whether leucovorin is given on day 1 only, versus on days 1 to 5.

Chemotherapy

Fluorouracil (5-FU) 370 mg/m² IV over 5 minutes once per day on days 1 to 5, given second
Leucovorin (Folinic acid) 200 mg/m² IV bolus once on day 1 (see note), given first

28-day cycle for 2 cycles, then 35-day cycles

Regimen variant #2, 2125/100

Study	Dates of enrollment	Evidence
Look et al. 1992	1989-09 to 1990-04	Phase 2

Chemotherapy

Fluorouracil (5-FU) 425 mg/m² IV once per day on days 1 to 5, given second
Leucovorin (Folinic acid) 20 mg/m² IV once per day on days 1 to 5, given first

28-day cycle for 2 cycles, then 35-day cycles

References

Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH; Gynecologic Oncology Group. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. link to original article PubMed
Look KY, Blessing JA, Gallup DG, Lentz SS; Gynecologic Oncology Group. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. link to original article contains dosing details in manuscript PubMed
Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA; Gynecologic Oncology Group. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. link to original article contains dosing details in manuscript PubMed

Gemcitabine monotherapy

Regimen variant #1

Study	Dates of enrollment	Evidence
Schilder et al. 2000 (GOG 127-K)	NR	Phase 2
Schilder et al. 2005	NR	Phase 2

Chemotherapy

Gemcitabine (Gemzar) 800 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (C)	Cemiplimab	Inferior OS
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

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

21-day cycles

References

GOG 127-K: Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS; Gynecologic Oncology Group. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Feb;76(2):204-7. link to original article contains dosing details in manuscript PubMed
Schilder RJ, Blessing J, Cohn DE; Gynecologic Oncology Group. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. link to original article contains dosing details in manuscript PubMed
EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
innovaTV 301: NCT04697628

Irinotecan monotherapy

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (C)	Cemiplimab	Inferior OS
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Irinotecan (Camptosar) 100 mg/m² IV once per day on days 1, 8, 15, 22

42-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Verschraegen et al. 1997	1993-1995	Phase 2
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV over 90 minutes once per day on days 1, 8, 15, 22

Supportive therapy

Diphenhydramine (Benadryl) 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion
Atropine (Atropen) 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
Loperamide (Imodium) 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions

42-day cycles

References

Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. link to original article contains dosing details in manuscript PubMed
EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
innovaTV 301: NCT04697628

Pembrolizumab monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Chung et al. 2019 (KEYNOTE-158_cervical)	2016-01-27 to 2016-08-18	Phase 2 (RT)

Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-158_cervical: Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Epub 2019 Apr 3. link to original article contains dosing details in abstract PubMed NCT02628067

Pemetrexed monotherapy

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (C)	Cemiplimab	Inferior OS
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Pemetrexed (Alimta) 500 mg/m² IV once on day 1

21-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence
Miller et al. 2008	2004-2006	Phase 2

Chemotherapy

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

Supportive therapy

Folic acid (Folate) 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 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

Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. link to original article contains dosing details in manuscript PubMed
EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
innovaTV 301: NCT04697628

Tisotumab vedotin monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Coleman et al. 2021 (innovaTV 204)	2018-06-12 to 2019-04-11	Phase 2 (RT)
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (E-RT-switch-ooc)	1a. Pemetrexed 1b. Topotecan 1c. Irinotecan 1d. Gemcitabine 1e. Vinorelbine	Superior OS (primary endpoint) Median OS: 11.5 vs 9.5 mo (HR 0.70, 95% CI 0.54-0.89)

Antibody-drug conjugate therapy

Tisotumab vedotin (Tivdak) 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1

21-day cycles

References

innovaTV 204: Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. Epub 2021 Apr 9. link to original article contains dosing details in abstract PubMed NCT03438396
innovaTV 301: NCT04697628

Topotecan monotherapy

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (C)	Cemiplimab	Inferior OS
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

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

21-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Dosing information is from CT.gov.

Chemotherapy

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

21-day cycles

References

EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
innovaTV 301: NCT04697628

Vinorelbine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Muggia et al. 2004	1997-1999	Phase 2		ORR: 14% (95% CI 5-27%)
Muggia et al. 2005	1997-1999	Phase 2		ORR: 7%
Tewari et al. 2022 (EMPOWER-Cervical 1)	2017-2020	Phase 3 (C)	Cemiplimab	Inferior OS
Awaiting publication (innovaTV 301)	2021-2023	Phase 3 (C)	Tisotumab vedotin	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

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

21-day cycles

References

Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. link to original article contains dosing details in manuscript PubMed
Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Jan;96(1):108-11. link to original article contains dosing details in manuscript PubMed
EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
innovaTV 301: NCT04697628

@@ 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 [[Cervical_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Cervical cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
-|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+|<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: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} variants 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.'''
+==[http://www.asco.org/ ASCO]==
+*'''2022:''' Chuang et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8920468/ Management and Care of Patients With Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update] [https://pubmed.ncbi.nlm.nih.gov/35245079/ PubMed]
+**'''2016:''' Chuang et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5493265/ Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/28717717/ PubMed]
+==[https://www.esmo.org/ ESMO]==
+*'''2018:''' Marth et al. [https://doi.org/10.1093/annonc/mdy160 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/29741577/ PubMed]
+**'''2017:''' Marth et al. [https://doi.org/10.1093/annonc/mdx220 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/28881916/ PubMed]
+**'''2012:''' Colombo et al. [https://doi.org/10.1093/annonc/mds268 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/22997451 PubMed]
+**'''2010:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdq162 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555099/ PubMed]
+**'''2009:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdp119 Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454454/ PubMed]
+**'''2008:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdn112 Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456752/ PubMed]
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426 NCCN Guidelines - Cervical Cancer]
+**'''2019:''' Koh et al. [https://doi.org/10.6004/Jnccn.2019.0001 Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/30659131/ PubMed]
+**'''2015:''' Koh et al. [https://doi.org/10.6004/jnccn.2015.0055 Cervical Cancer, Version 2.2015] [https://pubmed.ncbi.nlm.nih.gov/25870376/ PubMed]
+**'''2013:''' Koh et al. [https://doi.org/10.6004/Jnccn.2013.0043 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/23486458/ PubMed]
+**'''2010:''' Greer et al. [https://doi.org/10.6004/Jnccn.2010.0104 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/21147903/ PubMed]
+**'''2008:''' Greer et al. [https://doi.org/10.6004/Jnccn.2008.0003 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/18267056/ PubMed]
+**'''2004:''' Teng et al. [https://doi.org/10.6004/Jnccn.2004.0051 Cervical cancer guidelines. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19780304/ PubMed]
-=Chemoradiation=
+=Neoadjuvant chemotherapy=
-==Cisplatin & RT {{#subobject:89c649|Regimen=1}}==
+==Cisplatin & Paclitaxel {{#subobject:fdd2df|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7b5fcb|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.2003.09.015 Park et al. 2004]
+|2000-10 to 2002-01
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 12 and 6 hours prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 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
+*[[:Category:Emesis_prevention|Antiemetics]] before and 3 days after chemotherapy
+'''10-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Clinical response assessed after 3 cycles with pelvic examination and MRI. Treatment followed by [[Surgery#Cervical_cancer_surgery|surgery]] or radiation therapy.
+</div></div>
+===References===
+# Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. [https://doi.org/10.1016/j.ygyno.2003.09.015 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14751139/ PubMed]
+=Definitive therapy for locally advanced disease=
+==Brachytherapy protocol {{#subobject:ea73cc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen===
+To be completed
+====Radiotherapy====
+*[[Brachytherapy|Intracavitary brachytherapy with radium or its equivalent]] by the following study-specific criteria:
+**Pearcey et al. 2002: See paper for details
+**GOG 120, stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
+***Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy
+**B9E-MC-JHQS & Sehouli et al. 2012: 30 to 3500 cGy delivered to point A
+**GOG 219: 35 to 4360 cGy to point A
+**GOG 120, stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
+***Patients that could not receive brachytherapy underwent additional external_beam_radiotherapy for a total dose of 6120 cGy
+**GOG 123: 3000 cGy to point A for a total dose of 7500 cGy
+**GOG 165: ONE of the following:
+***Low-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 4000 cGy to point A given in 1 to 2 fractions
+***High-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
+**GOG 165: Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete
+</div></div>
+===References===
+# '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078]
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+==Carboplatin & RT {{#subobject:ea866d|Regimen=1}}==
+Carboplatin & RT: Carboplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1, Rose et al. 1999 & Rose et al. 2007 {{#subobject:63d249|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen variant #1, AUC-based carboplatin {{#subobject:e0ewe0|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]]
+|-
-Chemoradiation:
+|[https://doi.org/10.1016/s1470-2045(23)00479-5 Monk et al. 2023 (CALLA)]
-*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
+|2019-02-15 to 2020-12-10
-*Concurrent radiation therapy
+|style="background-color:#1a9851"|Phase 3 (C)
-**Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
+|1a. [[#Carboplatin.2C_Durvalumab.2C_RT_999|Carboplatin, Durvalumab, RT]]<br>1b. [[#Cisplatin.2C_Durvalumab.2C_RT_999|Cisplatin, Durvalumab, RT]]
-**Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
-'''6-week course'''
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
-Brachytherapy:
+====Chemotherapy====
-*Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
+*[[Carboplatin (Paraplatin)]] AUC 2 IV once per day on days 1, 8, 15, 22, 29
-*Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
+====Radiotherapy====
-**Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
+*Concurrent [[External_beam_radiotherapy|radiation therapy]], 180 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
+'''5-week course'''
-'''brachytherapy starts 1 to 3 weeks after external beam radiation'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
-===Regimen #2, Dueñas-González et al. 2011 {{#subobject:b23457|Variant=1}}===
+====Subsequent treatment====
-Level of Evidence:
+*[[#Brachytherapy_protocol|Brachytherapy]]
-<span
+</div></div><br>
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#eeeeee">
-padding:3px 6px 3px 6px;
+===Regimen variant #2, BSA-based carboplatin {{#subobject:e0e770|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]]
-Chemoradiation:
+!style="width: 20%"|Comparator
-*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, 1 to 2 hours before radiation
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy
+|-
+|[https://doi.org/10.1016/j.ygyno.2006.06.045 Veerasarn et al. 2006]
-'''6-week course'''
+|2001-2003
+|style="background-color:#1a9851"|Phase 3 (C)
-Brachytherapy:
+|[[#Carboplatin.2C_UFT.2C_RT_999|Carboplatin, UFT, RT]]
-*Brachytherapy with cesium-137, with 30-35 Gy delivered to point A
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of TTP/OS
+|-
-===Regimen #3, Lanciano et al. 2005 {{#subobject:ff6bdc|Variant=1}}===
+|}
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#00CD00;
+*[[Carboplatin (Paraplatin)]] 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, +/- 36
-padding:3px 6px 3px 6px;
+====Radiotherapy====
-border-color:black;
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]
-border-width:2px;
+'''5- to 6-week course'''
-border-style:solid;">Phase III</span>
+</div></div>
-Chemoradiation:
-*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum of 70 mg per dose) IV once per day on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
-*Concurrent radiation therapy, 1.8 Gy x 25 fractions, for an initial dose of 40.8 Gy
-*Brachytherapy involved:
-**EITHER Low-dose rate intracavitary brachytherapy of 40 Gy to point A given in 1 to 2 fractions
-**OR High-dose rate intracavitary brachytherapy of 30 Gy to point A given in 5 fractions, starting week 4 of XRT
-*Parametrial boost of 5.4-9 Gy was administered to the involved parametrium after whole pelvic RT was complete
 ===References===
-# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
+# Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P, Suntornpong N, Sangruchi S, Lertsanguansinchai P, Khorprasert C, Sookpreedee L, Udompunturak S. A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results. Gynecol Oncol. 2007 Jan;104(1):15-23. Epub 2006 Sep 25. [https://doi.org/10.1016/j.ygyno.2006.06.045 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16996583/ PubMed]
-# Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [http://jco.ascopubs.org/content/23/33/8289.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16230678 PubMed]
+# '''CALLA:''' Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. [https://doi.org/10.1016/s1470-2045(23)00479-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38039991/ PubMed] [https://clinicaltrials.gov/study/NCT03830866 NCT03830866]
-# '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
+==Cisplatin & RT {{#subobject:89c649|Regimen=1}}==
-# Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [http://jco.ascopubs.org/content/29/13/1678.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21444871 PubMed]
+Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
-==Cisplatin & RT -> Hysterectomy {{#subobject:7a88b3|Regimen=1}}==
+===Regimen variant #1, weekly cisplatin x 5, no cap + 4500 cGy {{#subobject:72453d|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| 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.22.02852 Kenter et al. 2023 (EORTC-55994)]
+|2002-05 to 2014-01
+|style="background-color:#1a9851"|Phase 3 (C)
+|Neoadjuvant chemotherapy, then surgery
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60
+|-
+|[https://doi.org/10.1016/s1470-2045(23)00479-5 Monk et al. 2023 (CALLA)]
+|2019-02-15 to 2020-12-10
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin.2C_Durvalumab.2C_RT_999|Carboplatin, Durvalumab, RT]]<br>1b. [[#Cisplatin.2C_Durvalumab.2C_RT_999|Cisplatin, Durvalumab, RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
+**Total number of fractions: 25
+**Total dose: 4500 cGy
+'''5-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, weekly cisplatin x 5, no cap + 5000 cGy {{#subobject:72d63d|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.radonc.2016.02.010 Lutgens et al. 2016 (RADCHOC)]
+|2003-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Hyperthermia_.26_RT_999|RT-HT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885185/ Shrivastava et al. 2018 (CRACx)]
+|2003-2011
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|RT]]
+| style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint)<br>OS60: 54% vs 46%<br>(HR 0.82, 95% CI 0.68-0.98)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+====Supportive therapy====
+*[[Ondansetron (Zofran)]] 16 mg (route not specified) once on day 1, prior to cisplatin
+*[[Dexamethasone (Decadron)]] 8 mg (route not specified) once on day 1, prior to cisplatin
+*Pre- and post- cisplatin [[:Category:Hydration|hydration]]
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
+**Total number of fractions: 25
+**Total dose: 5000 cGy
+'''5-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, weekly cisplatin x 6, no cap {{#subobject:63d249|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.2002.20.4.966 Pearcey et al. 2002]
+|1991-1996
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS36
+|-
+|rowspan=2|[https://doi.org/10.1056/NEJM199904153401502 Rose et al. 1999 (GOG 120)]
+|rowspan=2|1992-1997
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Hydroxyurea.2C_RT|Cisplatin, Fluorouracil, Hydroxyurea, RT]]
+|style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS
+|-
+|2. [[#Hydroxyurea_.26_RT|Hydroxyurea & RT]]
+|style="background-color:#1a9850"|Superior OS (co-primary endpoint)
+|-
+|[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_RT|Cisplatin, Gemcitabine, RT]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|[https://doi.org/10.1093/annonc/mdr628 Sehouli et al. 2012]
+|2003-2008
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_999|Carboplatin & Paclitaxel]], then [[Cervical_cancer_-_historical#Radiation_therapy|RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1200/jco.2013.50.1205 Zuliani et al. 2014]
+|2003-2010
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|RT]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>(HR 0.53, 95% CI 0.31-0.92)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912330/ DiSilvestro et al. 2014 (GOG 219)]
+|2006-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Tirapazamine.2C_RT_999|Cisplatin, Tirapazamine, RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ Yang et al. 2022]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Nedaplatin_.26_RT|Nedaplatin & RT]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|[https://doi.org/10.1016/s0140-6736(24)00317-9 Lorusson et al. 2024 (KEYNOTE-A18)]
+|2020-06-09 to 2022-12-15
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Pembrolizumab.2C_RT|Cisplatin, Pembrolizumab, RT]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br>
+''Note: In GOG 120, this regimen was intended for disease.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given 1 to 4 hours prior to radiation'''
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following study-specific criteria:
+**GOG 120, stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
+**GOG 219: 180 cGy x 23 to 25 fractions, for an initial dose of 41.4 to 4500 cGy
+**Pearcey et al. 2002 & Zuliani et al. 2014: 180 cGy x 25 fractions, for an initial dose of 4500 cGy
+**B9E-MC-JHQS & Sehouli et al. 2012: 180 cGy x 28 fractions, for an initial dose of 5040 cGy
+**GOG 120, stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy
+**Yang et al. 2022: 180 cGy/fraction/day, 5 days/week, a total of 25-28 fractions
+'''6-week course, followed in 1 to 3 weeks by:'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Sequential [[#Brachytherapy_protocol|brachytherapy]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, weekly cisplatin x 6, capped {{#subobject:ff6bdc|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/NEJM199904153401503 Keys et al. 1999 (GOG 123)]
+|1992-1997
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|RT]]
+|style="background-color:#1a9850"|Superior OS (co-primary endpoint)<br>OS36: 83% vs 74%<br>(RR 0.54, 95% CI 0.34-0.86)
+|-
+|[https://doi.org/10.1200/jco.2004.00.0497 Lanciano et al. 2005 (GOG 165)]
+|1997-2000
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Fluorouracil_.26_RT|Fluorouracil & RT]]
+|style="background-color:#d9ef8b"|Might have superior ORR (secondary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> (maximum dose of 70 mg) IV once per day on days 1, 8, 15, 22, 29, 36, '''given 4 hours before radiation'''
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
+**Total number of fractions: 25
+**Total dose: 4500 cGy
+'''6-week course, followed by:'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*GOG 123: Sequential [[#Brachytherapy_protocol|brachytherapy]], then adjuvant [[Surgery#Hysterectomy|hysterectomy]]
+*GOG 165: Sequential [[#Brachytherapy_protocol|brachytherapy]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, q3wk cisplatin x 3 {{#subobject:9a0b6f|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.ijrobp.2011.05.002 Ryu et al. 2011 (KCCH GY 1005)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]]; weekly cisplatin
+|style="background-color:#1a9850"|Superior OS60<br>OS60: 89% vs 66.5%<br>(HR 0.375, 95% CI 0.15-0.91)
 |-
-|[[#toc|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 1.8 to 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, (35 to 37)
+**Total number of fractions: 25 to 28
+**Total dose: 5000 cGy
+'''9-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details)
+</div></div>
+===References===
+# '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed]
+## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed]
+# '''GOG 123:''' Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [https://doi.org/10.1056/NEJM199904153401503 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202166/ PubMed]
+# '''NCIC-CTG:''' Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. [https://doi.org/10.1200/JCO.2002.20.4.966 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11844818/ PubMed]
+# '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078]
+<!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
+# '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]
+# '''KCCH GY 1005:''' Ryu SY, Lee WM, Kim K, Park SI, Kim BJ, Kim MH, Choi SC, Cho CK, Nam BH, Lee ED. Randomized clinical trial of weekly vs triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e577-81. Epub 2011 Aug 11. [https://doi.org/10.1016/j.ijrobp.2011.05.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21840137/ PubMed] [https://clinicaltrials.gov/study/NCT01097252 NCT01097252]
+# Sehouli J, Runnebaum IB, Fotopoulou C, Blohmer U, Belau A, Leber H, Hanker LC, Hartmann W, Richter R, Keyver-Paik MD, Oberhoff C, Heinrich G, du Bois A, Olbrich C, Simon E, Friese K, Kimmig R, Boehmer D, Lichtenegger W, Kuemmel S; NOGGO; AGO. A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Ann Oncol. 2012 Sep;23(9):2259-64. Epub 2012 Feb 21. [https://doi.org/10.1093/annonc/mdr628 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22357252/ PubMed]
+# '''GOG 219:''' DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. Epub 2014 Jan 6. [https://doi.org/10.1200/JCO.2013.51.4265 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912330/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24395863/ PubMed] [https://clinicaltrials.gov/study/NCT00262821 NCT00262821]
+#Zuliani AC, Esteves SC, Teixeira LC, Teixeira JC, de Souza GA, Sarian LO. Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized controlled trial. J Clin Oncol. 2014 Feb 20;32(6):542-7. Epub 2014 Jan 21. [https://doi.org/10.1200/jco.2013.50.1205 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24449243/ PubMed]
+##'''Update:''' Fachini AMD, Zuliani AC, Sarian LO, Teixeira JC, Esteves SCB, da Costa Machado H, Zeferino LC. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial. Gynecol Oncol. 2021 Feb;160(2):379-383. Epub 2020 Dec 16. [https://doi.org/10.1016/j.ygyno.2020.11.029 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33341239/ PubMed]
+# '''RADCHOC:''' Lutgens LC, Koper PC, Jobsen JJ, van der Steen-Banasik EM, Creutzberg CL, van den Berg HA, Ottevanger PB, van Rhoon GC, van Doorn HC, Houben R, van der Zee J. Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial. Radiother Oncol. 2016 Sep;120(3):378-382. Epub 2016 Feb 17. [https://doi.org/10.1016/j.radonc.2016.02.010 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26897513/ PubMed]
+# '''CRACx:''' Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: a randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2671607 link to original article] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29423520/ PubMed] [https://clinicaltrials.gov/study/NCT00193791 NCT00193791]
+#Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. [https://doi.org/10.1016/j.esmoop.2022.100565 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35994789/ PubMed] ChiCTR1800017108
+#'''EORTC-55994:''' Kenter GG, Greggi S, Vergote I, Katsaros D, Kobierski J, van Doorn H, Landoni F, van der Velden J, Reed N, Coens C, van Luijk I, Colombo N, Steen-Banasik EV, Ottevanger N, Casado A; EORTC-55994 Study Group. Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994. J Clin Oncol. 2023 Nov 10;41(32):5035-5043. Epub 2023 Sep 1. [https://doi.org/10.1200/jco.22.02852 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37656948/ PubMed] [https://clinicaltrials.gov/study/NCT00039338 NCT00039338]
+# '''CALLA:''' Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. [https://doi.org/10.1016/s1470-2045(23)00479-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38039991/ PubMed] [https://clinicaltrials.gov/study/NCT03830866 NCT03830866]
+#'''KEYNOTE-A18:''' Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. [https://doi.org/10.1016/s0140-6736(24)00317-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38521086/ PubMed] [https://clinicaltrials.gov/study/NCT04221945 NCT04221945]
+#'''NRG-GY006:''' [https://clinicaltrials.gov/study/NCT02466971 NCT02466971]
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+==Cisplatin, Pembrolizumab, RT {{#subobject:8pec49|Regimen=1}}==
+Cisplatin, Pembrolizumab, RT: Cisplatin, Pembrolizumab, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen {{#subobject:76bee5|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
-{| border="1" style="text-align:center;" !align="left"
+===Regimen {{#subobject:f6gc1c|Variant=1}}===
-|'''Study'''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Study
-|'''Comparator'''
+!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]]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJM199904153401503 Keys et al. 1999]
+|[https://doi.org/10.1016/s0140-6736(24)00317-9 Lorusson et al. 2024 (KEYNOTE-A18)]
-|<span
+|2020-06-09 to 2022-12-15
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
-padding:3px 6px 3px 6px;
+|[[#Cisplatin_.26_RT|Cisplatin & RT]]
-border-color:black;
+| style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>PFS24: 68% vs 57%<br>(HR 0.70, 95% CI 0.55-0.89)<br><br>Did not meet co-primary endpoint of OS
-border-width:2px;
-border-style:solid;">Phase III</span>
-|
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-====Chemoradiation====
+====Chemotherapy====
-*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum of 70 mg per dose) IV once per day on days 1, 8, 15, 22, 29, 36, '''4 hours before radiation'''
+*[[Cisplatin (Platinol)]] as follows:
-*Concurrent radiation therapy, 1.8 to 2 Gy given 5 days per week, for an initial dose of 45 Gy
+**Cycles 1 & 2: 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-**After external beam radiation, low-dose brachytherapy was administered, with 30 Gy to point A for a total dose of 75 Gy
+====Radiotherapy====
-*All patients proceeded to adjuvant hysterectomy
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] as follows:
+**Cycles 1 to 5: 200 mg IV once on day 1
+**Cycles 6 to 20: 400 mg IV once on day 1
+'''21-day cycle for 5 cycles, then 42-day cycle for 15 cycles'''
+</div></div>
 ===References===
-# Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401503 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202166 PubMed]
+#'''KEYNOTE-A18:''' Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. [https://doi.org/10.1016/s0140-6736(24)00317-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38521086/ PubMed] [https://clinicaltrials.gov/study/NCT04221945 NCT04221945]
-==Cisplatin, Fluorouracil, RT {{#subobject:7fff9b|Regimen=1}}==
+==Cisplatin & Fluorouracil (CF) & RT {{#subobject:7fff9b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+CF & RT: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 70/4000 x 4 {{#subobject:749e5d|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.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)]
+|1986-1990
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Hydroxyurea_.26_RT|Hydroxyurea & RT]]
+|style="background-color:#91cf60"|Seems to have superior OS (co-primary endpoint)<br>Median OS: NYR vs 59.8 mo<br>(RR 0.74, 90% CI 0.58-0.95)
+|-
+|[https://doi.org/10.1200/jco.2000.18.8.1606 Peters et al. 2000 (GOG 109/SWOG-8797)]
+|1991-1996
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]]
+|style="background-color:#1a9850"|Superior OS (co-primary endpoint)<br>OS48: 81% vs 71%<br>(HR 0.51)
 |-
-|[[#toc|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 22, 43, 64
-===Regimen {{#subobject:749e5d|Variant=1}}===
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1, 22, 43, 64 (total dose: 16,000 mg/m<sup>2</sup>)
-{| border="1" style="text-align:center;" !align="left"
+====Radiotherapy====
-|'''Study'''
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 170 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 39 (29 fractions, for a total dose of 4930 cGy)
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+**Patients with positive high common iliac lymph nodes also received 150 cGy x 30 fractions, for a total dose of 4500 cGy
-|'''Comparator'''
+'''12-week course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 75/4000 x 3 {{#subobject:16dd3c|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]]
 |-
-|[http://jco.ascopubs.org/content/18/8/1606.long Peters WA 3rd et al. 2000 (SWOG-8797)]
+|[https://doi.org/10.1056/NEJM199904153401501 Morris et al. 1999 (RTOG 9001)]
-|<span
+|1990-1997
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-padding:3px 6px 3px 6px;
+|[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]]
-border-color:black;
+|style="background-color:#1a9850"|Superior OS (primary endpoint)<br>OS60: 73% vs 58%
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Radiation_therapy|Radiation therapy]]
 |-
 |}
+''Note: radiation could start one day before chemotherapy, on "day 0".''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 70 mg/m2 IV over 2 hours once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 22, 43, '''given first'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (4000 mg/m2 total dose)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1, 22, 43 (total dose: 12,000 mg/m<sup>2</sup>)
+====Radiotherapy====
-'''21-day cycle x 4 cycles'''
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
+'''9-week course'''
-====Concurrent radiation therapy====
+</div>
-*Concurrent radiation therapy, 1.7 Gy x 29 fractions given 5 days per week, for a total dose of 49.3 Gy
+<div class="toccolours" style="background-color:#cbd5e7">
-**Patients with positive high common iliac lymph nodes also received 1.5 Gy x 30 fractions given 5 days per week, for a total dose of 45 Gy
+====Subsequent treatment====
+*[[#Brachytherapy_protocol|Brachytherapy]] (see paper for details)
-'''6-week course, started on cycle 1 day 1'''
+</div></div>
 ===References===
-# Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [http://jco.ascopubs.org/content/18/8/1606.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10764420 PubMed]
+# '''RTOG 9001:''' Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. [https://doi.org/10.1056/NEJM199904153401501 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202164/ PubMed]
+# '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517/ PubMed]
-==Cisplatin (Platinol), Fluorouracil (5-FU), Hydroxyurea (Hydrea), XRT, brachytherapy {{#subobject:670a50|Regimen=1}}==
+# '''GOG 109/SWOG-8797:''' Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [https://doi.org/10.1200/jco.2000.18.8.1606 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10764420/ PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT {{#subobject:670a50|Regimen=1}}==
+Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#c8a2c8">
+{| 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/NEJM199904153401502 Rose et al. 1999 (GOG 120)]
+|rowspan=2|1992-1997
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+|1. [[#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS
+|-
+|2. [[#Hydroxyurea_.26_RT|Hydroxyurea & RT]]
+|style="background-color:#1a9850"|Superior OS (co-primary endpoint)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:bc5f6d|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Definitive therapy {{#subobject:bc5f6d|Variant=1}}===
-<span
+<div class="toccolours" style="background-color:#b3e2cd">
-style="background:#00CD00;
+====Chemotherapy====
-padding:3px 6px 3px 6px;
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 29
-border-color:black;
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-border-width:2px;
+*[[Hydroxyurea (Hydrea)]] 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation on weeks 1 to 6'''
-border-style:solid;">Phase III</span>
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following stage-based criteria:
-Chemoradiation:
+**Stage IIB: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 25 (24 fractions, for an initial dose of 4080 cGy)
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once per day on days 1 & 29
+**Stage III or IVA: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (30 fractions, for an initial dose of 5100 cGy)
-*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV continuous infusion over 96 hours (4000 mg/m2 total dose) on days 1 to 4, 29-32
+'''5- to 6-week course, followed by:'''
-*[[Hydroxyurea (Hydrea)]] 2000 mg/m2 PO two times per week, 2 hours before radiation on weeks 1 to 6
+</div></div><br>
-*Concurrent radiation therapy
+<div class="toccolours" style="background-color:#eeeeee">
-**Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
+===Consolidation===
-**Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
-'''6-week course'''
+*Stage IIB patients received 4000 cGy by [[Brachytherapy|intracavitary brachytherapy]], for a total dose of 8080 cGy to point A
+*Stage III or IVA disease received 3000 cGy by [[Brachytherapy|intracavitary brachytherapy]], for a total dose of 8100 cGy to point A
-Brachytherapy:
+**Patients that could not receive brachytherapy underwent additional [[External_beam_radiotherapy|external beam radiation therapy]] for a total dose of 6120 cGy
-*Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
+'''One course'''
-*Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
+</div></div></div>
-**Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
-'''brachytherapy starts 1 to 3 weeks after external beam radiation'''
 ===References===
-# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
+# '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed]
-# '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
+## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed]
+==Cisplatin & Gemcitabine (GC) & RT {{#subobject:8df5df|Regimen=1}}==
-==Cisplatin, Gemcitabine, XRT, brachytherapy {{#subobject:8df5df|Regimen=1}}==
+Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:342f7f|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.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)]
+|2002-2004
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#91cf60"|Seems to have superior PFS (primary endpoint)<br>PFS36: 74.4% vs 65%<br>(HR 0.68, 95% CI 0.49-0.95)<br><br>Seems to have superior OS (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.68, 95% CI 0.49-0.95)
+|-
+|[https://doi.org/10.1093/annonc/mdt142 Cetina et al. 2013]
+|2004-2009
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:342f7f|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given first, 1 to 2 hours before radiation'''
-style="background:#00CD00;
+*[[Gemcitabine (Gemzar)]] 125 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 to 2 hours before radiation'''
-padding:3px 6px 3px 6px;
+====Radiotherapy====
-border-color:black;
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for an initial dose of 5040 cGy)
-border-width:2px;
-border-style:solid;">Phase III</span>
-Chemoradiation:
-*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given first, 1 to 2 hours before radiation
-*[[Gemcitabine (Gemzar)]] 125 mg/m2 IV over 30-60 minutes once per day on days 1, 8, 15, 22, 29, 36, given second, 1 to 2 hours before radiation
-*Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy
 '''6-week course'''
+</div>
-Brachytherapy:
+<div class="toccolours" style="background-color:#cbd5e7">
-*Brachytherapy with cesium-137, with 30-35 Gy delivered to point A
+====Subsequent treatment====
+*B9E-MC-JHQS: [[#Brachytherapy_protocol|Brachytherapy]] (30 to 3500 cGy delivered to point A), then adjuvant [[#Cisplatin_.26_Gemcitabine_.28GC.29|GC]], in 2 weeks
-Chemotherapy:
+*Cetina et al. 2013: [[#Brachytherapy_protocol|Brachytherapy]] verus [[Surgery#Radical_hysterectomy|radical hysterectomy]]
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1
+</div></div>
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
-'''21-day cycles x 2 cycles, to start 2 weeks after the end of brachytherapy'''
 ===References===
-# Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [http://jco.ascopubs.org/content/29/13/1678.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21444871 PubMed]
+<!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
+# '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]
-==Fluorouracil (5-FU), XRT {{#subobject:e9a589|Regimen=1}}==
+# Cetina L, González-Enciso A, Cantú D, Coronel J, Pérez-Montiel D, Hinojosa J, Serrano A, Rivera L, Poitevin A, Mota A, Trejo E, Montalvo G, Muñoz D, Robles-Flores J, de la Garza J, Chanona J, Jiménez-Lima R, Wegman T, Dueñas-González A. Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients. Ann Oncol. 2013 Aug;24(8):2043-7. Epub 2013 Apr 21. [https://doi.org/10.1093/annonc/mdt142 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23609186/ PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==Fluorouracil & RT {{#subobject:e9a589|Regimen=1}}==
+-FU & RT: '''<u>5-F</u>'''luouro'''<u>U</u>'''racil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#c8a2c8">
+{| 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.2004.00.0497 Lanciano et al. 2005 (GOG 165)]
+|1997-2000
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#fee08b"|Might have inferior ORR (secondary endpoint)
 |-
-|[[#toc|back to top]]
 |}
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Definitive therapy {{#subobject:38087d|Variant=1}}===
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#b3e2cd">
-padding:3px 6px 3px 6px;
+====Chemotherapy====
-border-color:black;
+*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29, 36 (total dose: 6750 mg/m<sup>2</sup>)
-border-width:2px;
+====Radiotherapy====
-border-style:solid;">Phase III</span>
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for an initial dose of 4080 cGy)
+'''6-week course, followed by:'''
-Chemoradiation:
+</div></div><br>
-*[[Fluorouracil (5-FU)]] 225 mg/m2/day IV continuous infusion over five days per week x 6 weeks
+<div class="toccolours" style="background-color:#eeeeee">
-*Concurrent radiation therapy, 1.8 Gy x 25 fractions, for an initial dose of 40.8 Gy
+===Consolidation===
-*Brachytherapy involved:
+<div class="toccolours" style="background-color:#b3e2cd">
-**EITHER Low-dose rate intracavitary brachytherapy of 40 Gy to point A given in 1 to 2 fractions
+====Radiotherapy====
-**OR High-dose rate intracavitary brachytherapy of 30 Gy to point A given in 5 fractions, starting week 4 of XRT
+**EITHER Low-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 4000 cGy to point A given in 1 to 2 fractions
-*Parametrial boost of 5.4-9 Gy was administered to the involved parametrium after whole pelvic RT was complete
+**OR High-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
+*Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete
+</div></div></div>
 ===References===
-# Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [http://jco.ascopubs.org/content/23/33/8289.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16230678 PubMed]
+# '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078]
+==Hydroxyurea & RT {{#subobject:b93f37|Regimen=1}}==
-==Hydroxyurea (Hydrea), XRT, brachytherapy {{#subobject:b93f37|Regimen=1}}==
+Hydroxyurea & RT: Hydroxyurea & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#c8a2c8">
+{| 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/10.1016/0360-3016(79)91209-4 Hreshchyshyn et al. 1979 (GOG 04)]
+|1970-1976
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]]
+|style="background-color:#91cf60"|Seems to have superior OS
+|-
+|[https://doi.org/10.1016/0002-9378(88)90499-1 Stehman et al. 1988 (GOG 56)]
+|1981-06 to 1985-12
+|style="background-color:#1a9851"|Randomized
+|[[#Misonidazole_.26_RT_999|Misonidazole & RT]]
+| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup>
+|-
+|[https://doi.org/10.1200/jco.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)]
+|1986-1990
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT|Cisplatin, Fluorouracil, RT]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|rowspan=2|[https://doi.org/10.1056/NEJM199904153401502 Rose et al. 1999 (GOG 120)]
+|rowspan=2|1992-1997
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#d73027"|Inferior OS
+|-
+|2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Hydroxyurea.2C_RT|Cisplatin, Fluorouracil, Hydroxyurea, RT]]
+|style="background-color:#d73027"|Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:176533|Variant=1}}===
+''<sup>1</sup>Reported efficacy for GOG 56 is based on the 1993 update.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Definitive therapy {{#subobject:176533|Variant=1}}===
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#b3e2cd">
-padding:3px 6px 3px 6px;
+====Chemotherapy====
-border-color:black;
+*[[Hydroxyurea (Hydrea)]] as follows:
-border-width:2px;
+**Weeks 1 to 6: 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation'''
-border-style:solid;">Phase III</span>
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following stage-based criteria:
-Chemoradiation:
+**Stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
-*[[Hydroxyurea (Hydrea)]] 2000 mg/m2 PO two times per week, 2 hours before radiation on weeks 1 to 6
+**Stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy
-*Concurrent radiation therapy
+'''7- to 9-week course'''
-**Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
+</div></div><br>
-**Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
+<div class="toccolours" style="background-color:#eeeeee">
+===Consolidation===
-'''6-week course'''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
-Brachytherapy:
+*[[Brachytherapy|Intracavitary brachytherapy]] by the following stage-based criteria:
-*Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
+**Stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
-*Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
+*Stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
-**Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
+*Patients that could not receive brachytherapy underwent additional [[External_beam_radiotherapy|external beam radiation therapy]] for a total dose of 6120 cGy
+</div></div></div>
-'''brachytherapy starts 1 to 3 weeks after external beam radiation'''
 ===References===
-# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
+# Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA. Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys. 1979 Mar;5(3):317-22. [https://doi.org/10.1016/0360-3016(79)91209-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/110744/ PubMed]
-# '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
+# '''GOG 56:''' Stehman FB, Bundy BN, Keys H, Currie JL, Mortel R, Creasman WT. A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix: A preliminary report of a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1988 Jul;159(1):87-94. [https://doi.org/10.1016/0002-9378(88)90499-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3293456/ PubMed]
+##'''Update:''' Stehman FB, Bundy BN, Thomas G, Keys HM, d'Ablaing G 3rd, Fowler WC Jr, Mortel R, Creasman WT. Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial. J Clin Oncol. 1993 Aug;11(8):1523-8. [https://doi.org/10.1200/jco.1993.11.8.1523 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8336190/ PubMed]
+# '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed]
+## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed]
+# '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517/ PubMed]
-==Radiation therapy {{#subobject:b13dbe|Regimen=1}}==
+==Nedaplatin & RT {{#subobject:igjz49|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+Nedaplatin & RT: Nedaplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:638icz|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/pmc9588898/ Yang et al. 2022]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]]
+| style="background-color:#1a9850" |Superior PFS36 (primary endpoint)<br>Median PFS: 30 vs 28 mo<br>(HR 0.25, 95% CI 0.08-0.77)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:98b535|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Nedaplatin (Aqupla)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, +/- 36
-style="background:#00CD00;
+====Radiotherapy====
-padding:3px 6px 3px 6px;
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day, 5 days/week, a total of 25-28 fractions
-border-color:black;
+</div></div>
-border-width:2px;
-border-style:solid;">Phase III</span>
-''Demonstrably inferior; here for reference purposes only.''
 ===References===
-# Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401503 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202166 PubMed]
+#Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. [https://doi.org/10.1016/j.esmoop.2022.100565 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35994789/ PubMed] ChiCTR1800017108
-# Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [http://jco.ascopubs.org/content/18/8/1606.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10764420 PubMed]
-=Neoadjuvant chemotherapy=
+=Adjuvant therapy=
-==Cisplatin & Paclitaxel {{#subobject:fdd2df|Regimen=1}}==
+==Carboplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:93caff|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.2010.30.4899 Blohmer et al. 2011 (NOGGO-AGO)]
+|1999-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Complex_multipart_regimens#NOGGO-AGO|See link]]
+| style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]]
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:7b5fcb|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-{| border="1" style="text-align:center;" !align="left"
+<div class="toccolours" style="background-color:#cbd5e8">
-|'''Study'''
+====Preceding treatment====
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+*[[Surgery#Radical_hysterectomy|Wertheim-Meigs radical abdominal hysterectomy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 4 IV over 60 minutes once on day 1
+*[[Ifosfamide (Ifex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3, with mesa
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3, with ifosfamide
+'''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Cervical_cancer_-_historical#Radiation_therapy_2|Pelvic EBRT]] x 5040 cGy
+</div></div>
+===References===
+# '''NOGGO-AGO:''' Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed]
+==Cisplatin & Gemcitabine (GC) {{#subobject:5de31f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:c4c8f2|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]]
 |-
-|[http://www.gynecologiconcology-online.net/article/S0090-8258(03)00647-4/abstract Park et al. 2004]
+|[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)]
-|<span
+|2002-2004
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*Definitive [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_RT|Cisplatin, Gemcitabine, RT]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''21-day cycle for 2 cycles'''
+</div></div>
-*[[Cisplatin (Platinol)]] 60 mg/m2 IV over 2 hours on day 1, '''given second'''
-*[[Paclitaxel (Taxol)]] 60 mg/m2 IV over 3 hours on day 1, '''given first'''
-Supportive medications:
-*[[Dexamethasone (Decadron)]] 20 mg PO 12 and 6 hours before paclitaxel
-*Cimetidine (Tagamet) 300 mg IV 30 minutes prior to paclitaxel
-*Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
-*[[antiemesis|Antiemetics]] before and 3 days after chemotherapy
-'''10-day cycle x 3 cycles'''
-*Clinical response assessed after 3 cycles with pelvic examination and MRI
 ===References===
-# Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. [http://www.gynecologiconcology-online.net/article/S0090-8258(03)00647-4/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14751139 PubMed]
+<!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
+# '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]
+==Radiation therapy {{#subobject:e34211|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:aa4d8e|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.2010.30.4899 Blohmer et al. 2011 (NOGGO-AGO)]
+|1999-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Complex_multipart_regimens#NOGGO-AGO|See link]]
+| style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]]
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Cervical_cancer_surgery|Surgery]], then adjuvant [[#Carboplatin_.26_Ifosfamide|Carboplatin & Ifosfamide]] x 4
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*[[External beam radiotherapy]]: 180 cGy for 28 fractions, for a total dose of 5040 cGy
+*If resection margins positive, patients received one of the following:
+**EBRT boost of 2 x 500 cGy
+**Low-dose brachytherapy
+'''6-week course'''
+</div></div>
+===References===
+# '''NOGGO-AGO:''' Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed]
-=Metastatic disease=
+=Persistent, recurrent, or metastatic disease, first-line therapy=
-==Bevacizumab (Avastin) {{#subobject:1da8f9|Regimen=1}}==
+==ABCP {{#subobject:bcc235|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+ABCP: '''<u>A</u>'''tezolizumab, '''<u>B</u>'''evacizumab, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:76uty4|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(23)02405-4 Oaknin et al. 2023 (BEATcc)]
+|2018-10-08 to 2021-08-20
+|style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 32.1 vs 22.8 mo<br>(HR 0.68, 95% CI 0.52-0.88)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 13.7 vs 10.4 mo<br>(HR 0.62, 95% CI 0.49-0.78)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:67b93c|Variant=1}}===
+''Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
-padding:3px 6px 3px 6px;
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-border-color:black;
+====Immunotherapy====
-border-width:2px;
+*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
-border-style:solid;">Phase II</span>
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. [http://jco.ascopubs.org/content/27/7/1069.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19139430 PubMed]
+#'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839]
-==Carboplatin (Paraplatin) {{#subobject:fae1e7|Regimen=1}}==
+==Carboplatin monotherapy {{#subobject:fae1e7|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:fe1b36|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/10.1016/0090-8258(90)90262-j Weiss et al. 1990]
+|NR
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:fe1b36|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV once on day 1
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] 400 mg/m2 IV on day 1
 '''28-day cycles'''
+</div></div>
 ===References===
-# Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. [http://www.ncbi.nlm.nih.gov/pubmed/2258080 PubMed]
+# Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS; [[Study_Groups#SWOG|SWOG]]. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. [https://doi.org/10.1016/0090-8258(90)90262-j link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2258080/ PubMed]
 ==Carboplatin & Docetaxel {{#subobject:39c86d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 6 cycles {{#subobject:9fb5d5|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://ijgc.bmj.com/content/20/9/1563.abstract Takekida et al. 2010]
+|2004-01 to 2005-12
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second'''
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]]
+*[[Ondansetron (Zofran)]] or [[Granisetron]]
+*[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia
+'''21-day cycle for up to 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, indefinite {{#subobject:9ce265|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.2004.11.044 Nagao et al. 2005]
+|2001-2004
+|style="background-color:#ffffbe"|Pilot, fewer than 20 pts
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second'''
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]]
+*[[Ondansetron (Zofran)]] or [[Granisetron]]
+*[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia
+'''21-day cycles'''
+</div></div>
+===References===
+# Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer: a pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [https://doi.org/10.1016/j.ygyno.2004.11.044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15721429/ PubMed]
+# Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. [https://ijgc.bmj.com/content/20/9/1563.abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/21370599/ PubMed]
+==Carboplatin & Paclitaxel (CP) {{#subobject:be30d5|Regimen=1}}==
+TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7668ec|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://ijgc.bmj.com/content/19/4/777-781.abstract Pectasides et al. 2009a]
+|NR
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)]
+|2006-2009
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#eeee01"|Non-inferior OS (primary endpoint)<br>Median OS: 17.5 vs 18.3 mo<br>(HR 0.994, 90% CI 0.79-1.25)
+|-
+|[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:9fb5d5|Variant=1}}===
+''Note: Pectasides et al. 2009a allowed the regimen to be given up to 9 cycles. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
-padding:3px 6px 3px 6px;
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-border-color:black;
+'''21-day cycle for 6 or more cycles (see note)'''
-border-width:2px;
+</div></div>
-border-style:solid;">Phase II</span>
+===References===
+# Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. [https://ijgc.bmj.com/content/19/4/777-781.abstract link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19509587/ PubMed]
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 1 hour on day 1, given second
+# '''JCOG0505:''' Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.58.4391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732161/ PubMed] [https://clinicaltrials.gov/study/NCT00295789 NCT00295789]
-*[[Docetaxel (Taxotere)]] 60 mg/m2 IV over 1 hour on day 1, given first
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+==Carboplatin & Paclitaxel (CP) & Bevacizumab {{#subobject:be3165|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:76615h|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/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)]
+|2018-10-08 to 2021-08-20
+|style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#ABCP|ABCP]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Atezolizumab.2C_Bevacizumab|Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab]]
+| style="background-color:#d73027" |Inferior PFS/OS
+|-
+|}
+''Note: In KEYNOTE-826, the decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6 (see note): AUC 5 IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 '''21-day cycles'''
+</div></div>
-Supportive medications:
-*[[Dexamethasone (Decadron)]]
-*Ondansetron or granisetron for [[antiemesis]]
-*[[Filgrastim (Neupogen)]] 5 mcg/kg daily for patients with grade 4 neutropenia or febrile neutropenia
 ===References===
-# Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer. A pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [http://www.sciencedirect.com/science/article/pii/S0090825804009758 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15721429 PubMed]
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
-# Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. [http://www.ncbi.nlm.nih.gov/pubmed/21370599 PubMed]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+#'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839]
-==Carboplatin & Paclitaxel {{#subobject:be30d5|Regimen=1}}==
+==Carboplatin & Paclitaxel (CP), Bevacizumab, Pembrolizumab {{#subobject:yh2n65|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ug81uh|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/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:7668ec|Variant=1}}===
+''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br>
-Level of Evidence:
+''Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
-<span
+<div class="toccolours" style="background-color:#b3e2cd">
-style="background:#EEEE00;
+====Chemotherapy====
-padding:3px 6px 3px 6px;
+*[[Carboplatin (Paraplatin)]] as follows:
-border-color:black;
+**Cycles 1 to 6 (see note): AUC 5 IV once on day 1
-border-width:2px;
+*[[Paclitaxel (Taxol)]] as follows:
-border-style:solid;">Phase II</span>
+**Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 1 hour on day 1
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours on day 1
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] as follows:
-'''21-day cycles x 6 to 9 cycles'''
+**Cycles 1 up to 35: 200 mg IV once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# Moore KN, Herzog TJ, Lewin S, Giuntoli RL, Armstrong DK, Rocconi RP, Spannuth WA, Gold MA. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007 May;105(2):299-303. Epub 2007 Feb 14. [http://www.sciencedirect.com/science/article/pii/S009082580600970X link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17303230 PubMed]
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
-# Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. [http://journals.lww.com/ijgc/pages/articleviewer.aspx?year=2009&issue=05000&article=00049&type=abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19509587 PubMed]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
-==Cisplatin (Platinol) {{#subobject:117c0b|Regimen=1}}==
+==Carboplatin & Paclitaxel (CP) & Pembrolizumab {{#subobject:ch10d5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ag7nec|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/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77)
 |-
-|[[#toc|back to top]]
 |}
+''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br>
+''Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] as follows:
+**Cycles 1 to 6 (see note): AUC 5 IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
+===References===
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+==Cisplatin monotherapy {{#subobject:117c0b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a3542f|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|'''Study'''
+!style="width: 20%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Dates of enrollment
-|'''Comparator'''
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://pubmed.ncbi.nlm.nih.gov/498154 Thigpen et al. 1979a]
+|NR in abstract
+| style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.1985.3.8.1079 Bonomi et al. 1985 (GOG 43)]
+|1978-1982
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose<br>2. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose, split doses
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1016/s0090-8258(89)80033-2 Thigpen et al. 1989 (GOG 64)]
+|1982-1985
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_monotherapy|Cisplatin]]; CI
+| style="background-color:#ffffbf" |Did not meet primary efficacy endpoints
+|-
+|rowspan=2|[https://doi.org/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)]
+|rowspan=2|1990-1994
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_.26_Ifosfamide|Cisplatin & Ifosfamide]]
+|style="background-color:#d73027"|Inferior PFS
+|-
+|2. [[#Cisplatin_.26_Mitolactol_999|Cisplatin & Mitolactol]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1023/a:1011165115426 Vermorken et al. 2001]
+|1986-1991
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#BEMP_999|BEMP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1200/jco.2004.04.170 Moore et al. 2004 (GOG 169)]
+|1997-1999
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#d73027"|Inferior PFS
 |-
-|[http://jco.ascopubs.org/content/22/15/3113.long Moore et al. 2004]
+|rowspan=2|[https://doi.org/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)]
-|<span
+|rowspan=2|1999-2002
-style="background:#00CD00;
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|1. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
-border-color:black;
+|style="background-color:#fc8d59"|Seems to have inferior OS
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
 |-
-!colspan="4" align="center"|
+|2. [[#MVAC_999|MVAC]]
+|style="background-color:#d3d3d3"|Not reported
 |-
-|[http://jco.ascopubs.org/content/23/21/4626.long Long et al. 2005]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6162273/ Aoki et al. 2018 (Taiho 10020380)]
-|<span
+|2008-2011
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[#Cisplatin_.26_S-1_999|Cisplatin & S-1]]
-border-color:black;
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles; if not responding, given for maximum of 6 cycles'''
+</div></div>
 ===References===
-# Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [http://jco.ascopubs.org/content/22/15/3113.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15284262 PubMed]
+# Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J; Gynecologic Oncology Group. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1549-55. [https://pubmed.ncbi.nlm.nih.gov/498154/ PubMed]
-# Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/21/4626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15911865 PubMed]
+# '''GOG 43:''' Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. [https://doi.org/10.1200/JCO.1985.3.8.1079 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3894589/ PubMed]
+# '''GOG 64:''' Thigpen JT, Blessing JA, DiSaia PJ, Fowler WC Jr, Hatch KD. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1989 Feb;32(2):198-202. [https://doi.org/10.1016/s0090-8258(89)80033-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2910782/ PubMed]
-==Cisplatin & Gemcitabine {{#subobject:fbbad7|Regimen=1}}==
+# '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8996138/ PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+# Vermorken JB, Zanetta G, Freire de Oliveira C, van der Burg ME, Lacave AJ, Teodorovic I, Boes GH, Colombo N; [[Study_Groups#EORTC|EORTC]] Gynecological Cancer Cooperative Group. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol. 2001 Jul;12(7):967-74. [https://doi.org/10.1023/a:1011165115426 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11521804/ PubMed]
+# '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284262/ PubMed]
+<!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. -->
+# '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15911865/ PubMed] [https://clinicaltrials.gov/study/NCT00003945 NCT00003945]
+# '''Taiho 10020380:''' Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, Katsumata N, Cha SD, Kim JH, Kim BG, Hirashima Y, Fujiwara K, Kim YT, Kim SM, Chung HH, Chang TC, Kamura T, Takizawa K, Takeuchi M, Kang SB. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer. 2018 Aug;119(5):530-537. Epub 2018 Aug 3. [https://doi.org/10.1038/s41416-018-0206-7 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6162273/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30072745/ PubMed] [https://clinicaltrials.gov/study/NCT00770874 NCT00770874]
+==Cisplatin & Gemcitabine (GC) {{#subobject:fbbad7|Regimen=1}}==
+GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:2e2004|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=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)]
+|rowspan=3|2003-2007
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior PFS (secondary endpoint)
 |-
-|[[#toc|back to top]]
+|2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
-|}
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-===Regimen #1 {{#subobject:2e2004|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
 |-
-|[http://jco.ascopubs.org/content/27/28/4649.long Monk et al. 2009]
+|3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]]
-|<span
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br> [[Cervical_cancer#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]<br> [[Cervical_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1
+====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
-===Regimen #2 {{#subobject:777e52|Variant=1}}===
+===References===
-{| border="1" style="text-align:center;" !align="left"
+<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
-|'''Study'''
+# '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+==Cisplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:93caff|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/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)]
+|rowspan=2|1990-1994
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+|1. [[#Cisplatin_monotherapy|Cisplatin]]
+| style="background-color:#1a9850" |Superior PFS (secondary endpoint)
+|-
+|2. [[#Cisplatin_.26_Mitolactol_777|Cisplatin & Mitolactol]]
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[http://www.gynecologiconcology-online.net/article/S0090-8258(05)00789-4/abstract Brewer et al. 2006]
+|[https://doi.org/10.1200/JCO.2002.07.045 Bloss et al. 2002 (GOG 149)]
-|<span
+|1994-1997
-style="background:#EEEE00;
+|style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[Stub#CIB|CIB]]
-border-color:black;
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cisplatin (Platinol)]] 30 mg/m2 IV once on day 1, '''given first'''
+====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 800 mg/m2 IV once per day on days 1 & 8, '''given second'''
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 concurrent with mesna
-'''28-day cycles'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 6000 mg/m<sup>2</sup> IV continuous infusion over 36 hours, started on day 1 concurrent with ifosfamide
+'''21-day cycle for up to 6 cycles'''
+</div></div>
 ===References===
-# Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. [http://www.gynecologiconcology-online.net/article/S0090-8258(05)00789-4/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16271750 PubMed]
+# '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8996138/ PubMed]
-# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+# '''GOG 149:''' Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, Markman M, Benda J. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2002 Apr 1;20(7):1832-7. [https://doi.org/10.1200/JCO.2002.07.045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11919241/ PubMed]
 ==Cisplatin & Mitomycin {{#subobject:c97b6f|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:6e84ee|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/10.1016/s0959-8049(01)00178-2 Wagenaar et al. 2001]
+|NR
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#8c96c6" |ORR: 42% (95% CI: 26-61%)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:6e84ee|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second'''
-style="background:#EEEE00;
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV push once on day 1, '''given first'''
-padding:3px 6px 3px 6px;
+====Supportive therapy====
-border-color:black;
+*1 liter NS over 1 hour once on day 1, prior to chemotherapy, then 1 liter NS over 1 hour once on day 1, after cisplatin
-border-width:2px;
+*[[Furosemide (Lasix)]] (route/dose not specified) once on day 1, prior to chemotherapy
-border-style:solid;">Phase II</span>
+*[[Mannitol]] IV push once on day 1, prior to cisplatin
+'''28-day cycle for 9 cycles'''
-''Note: The NCCN, Cervical Cancer version 1.2012, lists mitomycin monotherapy as a potential second-line therapy option, and cites the reference below, which describes a two-drug regimen.  No primary reference for the monotherapy regimen could be found.''
+</div></div>
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1, given second
-*[[Mitomycin (Mutamycin)]] 6 mg/m2 IV push on day 1, given first
-'''28-day cycles x 9 cycles'''
-Supportive hydration:
-*1 liter NS over 1 hour and furosemide before chemotherapy, and 1 liter NS over 1 hour after cisplatin
-*Mannitol IV push prior to cisplatin
 ===References===
-# Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. [http://www.ejcancer.info/article/S0959-8049%2801%2900178-2/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11527687 PubMed]
+# Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Gynecological Cancer Group. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix: a European Organisation for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. [https://doi.org/10.1016/s0959-8049(01)00178-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11527687/ PubMed]
 ==Cisplatin & Paclitaxel {{#subobject:aab02e|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''isplatin
+<br>CP: '''<u>C</u>'''isplatin & '''<u>P</u>'''aclitaxel
+<br>TP: '''<u>T</u>'''axol (Paclitaxel) & '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 50/135, 3 hr paclitaxel {{#subobject:PYV4|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=3|[https://doi.org/10.1056/NEJMoa1309748 Tewari et al. 2014 (GOG 240)]
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
+|-
+|2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:bd6f7b|Variant=1}}===
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''
-{| border="1" style="text-align:center;" !align="left"
+<div class="toccolours" style="background-color:#b3e2cd">
-|'''Study'''
+====Chemotherapy====
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
-|'''Comparator'''
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycles until CR or indefinitely'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 50/135, CI paclitaxel {{#subobject:bd6f7b|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.2004.04.170 Moore et al. 2004 (GOG 169)]
+|1997-1999
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Cisplatin_monotherapy|Cisplatin]]
+|style="background-color:#1a9850"|Superior PFS (secondary endpoint)<br><br>Superior ORR (primary endpoint)
+|-
+|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)]
+|rowspan=3|2003-2007
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
+|style="background-color:#91cf60"|Seems to have superior PFS (secondary endpoint)
 |-
-|[http://jco.ascopubs.org/content/22/15/3113.long Moore et al. 2004]
+|2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
-|<span
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.28Platinol.29|Cisplatin]]
 |-
-!colspan="4" align="center"|
+|3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]]
+|style="background-color:#d9ef8b"|Might have superior PFS (secondary endpoint)
 |-
-|[http://jco.ascopubs.org/content/27/28/4649.long Monk et al. 2009]
+|[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)]
-|<span
+|2006-2009
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]
-border-color:black;
+|style="background-color:#eeee01"|Non-inferior OS
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]<br> [[Cervical_cancer#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]<br> [[Cervical_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
 |-
 |}
+''Note: patients in JCOG0505 received a maximum of 6 cycles.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 2
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+====Supportive therapy====
+*(varies depending on reference):
+*[[Dexamethasone (Decadron)]]
+*[[Diphenhydramine (Benadryl)]]
+*H2 receptor antagonist such as [[Cimetidine (Tagamet)]] or [[Ranitidine (Zantac)]]
+*Prophylactic [[:Category:Emesis_prevention|antiemetics]]
+*"Adequate IV [[:Category:Hydration|hydration]] and electrolyte replacement"
+'''21-day cycles; if not responding, given for maximum of 6 cycles.'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 2
+===Regimen variant #3, 50/175 {{#subobject:ccc92b|Variant=1}}===
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV continuous infusion over 24 hours 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]]
+|-
+|rowspan=3|[https://doi.org/10.1056/NEJMoa1309748 Tewari et al. 2014 (GOG 240)]
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
+|-
+|2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br>
+''Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
+<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 once on day 1
+'''21-day cycle for 6 or more cycles (see note)'''
+</div></div>
+===References===
+# '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284262/ PubMed]
+<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
+# '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077]
+# '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062]
+## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed]
+## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed]
+# '''JCOG0505:''' Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.58.4391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732161/ PubMed] [https://clinicaltrials.gov/study/NCT00295789 NCT00295789]
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+==Cisplatin, Paclitaxel, Bevacizumab {{#subobject:PYR1|Regimen=1}}==
+CP+Bev: '''<u>C</u>'''isplatin, '''<u>P</u>'''aclitaxel, '''<u>Bev</u>'''acizumab
+{| class="wikitable" style="color:black; background-color:#42f584"
+|<small>'''ESMO-preferred (I-A, 2017)'''</small>
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 135 mg/m<sup>2</sup> paclitaxel {{#subobject:PYV1|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=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 16.8 vs 13.3 mo<br>(HR 0.77, 95% CI 0.62-0.95)
+|-
+|2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup>
+|-
+|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles until CR or indefinitely'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 175 mg/m<sup>2</sup> paclitaxel {{#subobject:ca025d|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=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 16.8 vs 13.3 mo<br>(HR 0.77, 95% CI 0.62-0.95)
+|-
+|2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup>
+|-
+|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)]
+|2018-10-08 to 2021-08-20
+|style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#ABCP|ABCP]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Atezolizumab.2C_Bevacizumab|Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab]]
+| style="background-color:#d73027" |Inferior PFS/OS
+|-
+|}
+''<sup>1</sup>Reported efficacy for this comparison in GOG 240 is based on the 2017 update.''<br>
+''Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. The decision to give bevacizumab in KEYNOTE-826 was at the discretion of the treating institution and was not a randomization.''
+<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 once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycle for 6 or more cycles (see note)'''
+</div></div>
+===References===
+# '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062]
+## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed]
+## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed]
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+#'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839]
-Supportive medications (varies depending on reference):
+==Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab {{#subobject:bcc2hw|Regimen=1}}==
-*[[Dexamethasone (Decadron)]], [[Diphenhydramine (Benadryl)]], H2 receptor antagonist (such as [[Cimetidine (Tagamet)]] or [[Ranitidine (Zantac)]]), and prophylactic [[Antiemesis|antiemetics]].
+<div class="toccolours" style="background-color:#eeeeee">
-*"Adequate IV hydration and electrolyte replacement"
+===Regimen {{#subobject:51hby4|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(23)02405-4 Oaknin et al. 2023 (BEATcc)]
+|2018-10-08 to 2021-08-20
+|style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 32.1 vs 22.8 mo<br>(HR 0.68, 95% CI 0.52-0.88)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 13.7 vs 10.4 mo<br>(HR 0.62, 95% CI 0.49-0.78)
+|-
+|}
+''Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.''
+<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 once on day 1
+====Immunotherapy====
+*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+#'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839]
-'''21-day cycles; if not responding, given for maximum of 6 cycles'''
+==Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab {{#subobject:gac765|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:18ghuh|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/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br>
+''Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycles 1 to 6 (see note): 50 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] as follows:
+**Cycles 1 up to 35: 200 mg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
+==Cisplatin, Paclitaxel, Pembrolizumab {{#subobject:chge55|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:aggc1h|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/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br>
+''Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycles 1 to 6 (see note): 50 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
 ===References===
-# Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [http://jco.ascopubs.org/content/22/15/3113.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15284262 PubMed]
+#'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567]
-# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed]
+##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed]
 ==Cisplatin & Topotecan {{#subobject:e399c6|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+TC: '''<u>T</u>'''opotecan & '''<u>C</u>'''isplatin
+<br>CT: '''<u>C</u>'''isplatin & '''<u>T</u>'''opotecan
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:f703f4|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/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)]
+|rowspan=2|1999-2002
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Cisplatin_monotherapy|Cisplatin]]
+|style="background-color:#91cf60"|Seems to have superior OS (primary endpoint)<br>Median OS: 9.4 vs 6.5 mo<br>(RR 0.76, 95% CI 0.59-0.98)
+|-
+|2. [[#MVAC_999|MVAC]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)]
+|rowspan=3|2003-2007
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|2. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1007/s12032-010-9700-3 Coronel et al. 2010 (006/027/ICI)]
+|2007-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Topotecan.2C_Hydralazine.2C_Valproate_888|CT + HV]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:f703f4|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-{| border="1" style="text-align:center;" !align="left"
+====Chemotherapy====
-|'''Study'''
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+*[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3, '''given first'''
-|'''Comparator'''
+'''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+<!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. -->
+# '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15911865/ PubMed] [https://clinicaltrials.gov/study/NCT00003945 NCT00003945]
+<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
+# '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077]
+# '''006/027/ICI:''' Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M, Vidal S, Dueñas-González A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer: preliminary results. Med Oncol. 2011 Dec;28 Suppl 1:S540-6. Epub 2010 Oct 8. [https://doi.org/10.1007/s12032-010-9700-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20931299/ PubMed] [https://clinicaltrials.gov/study/NCT00532818 NCT00532818]
+==Cisplatin & Vinorelbine (CVb) {{#subobject:176775|Regimen=1}}==
+CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine
+<br>VC: '''<u>V</u>'''inorelbine, '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e442f7|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]]
 |-
-|[http://jco.ascopubs.org/content/23/21/4626.long Long et al. 2005]
+|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)]
-|<span
+|rowspan=3|2003-2007
-style="background:#00CD00;
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-padding:3px 6px 3px 6px;
+|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
-border-color:black;
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.28Platinol.29|Cisplatin]]
 |-
-!colspan="4" align="center"|
+|2. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#fee08b"|Might have inferior PFS (primary endpoint)
 |-
-|[http://jco.ascopubs.org/content/27/28/4649.long Monk et al. 2009]
+|3. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
-|<span
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]<br> [[Cervical_cancer#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>  [[Cervical_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1, '''given second'''
+====Chemotherapy====
-*[[Topotecan (Hycamtin)]] 0.75 mg/m2 IV over 30 minutes once per day on days 1 to 3, '''given first'''
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles; if not responding, given for maximum of 6 cycles'''
+</div></div>
+===References===
+<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
+# '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077]
+==Ifosfamide monotherapy {{#subobject:1d18ed|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:962339|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/10.1007/BF00273403 Coleman et al. 1986]
+|NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1006/gyno.1993.1084 Sutton et al. 1993b]
+|1985-07 to 1990-12
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1016/s0002-9378(12)90824-8 Sutton et al. 1993a]
+|1988-01 to 1990-02
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]] by the following exposure-based criteria:
+*No previous pelvic radiation or other chemotherapy: 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*Previous pelvic radiation or other chemotherapy: 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5
+====Supportive therapy====
+*[[Mesna (Mesnex)]] at 20% of ifosfamide dose (for example, 300 mg/m<sup>2</sup> for 1500 mg/m<sup>2</sup> dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*[[Ifosfamide (Ifex)]] dose could be increased by 300 mg/m<sup>2</sup> or decreased by 20% depending on toxicity
+</div></div>
+===References===
+# Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, Wiltshaw E. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. [https://doi.org/10.1007/BF00273403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3802384/ PubMed]
+# Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY; Gynecologic Oncology Group. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. [https://doi.org/10.1016/s0002-9378(12)90824-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8456884/ PubMed]
+# Sutton GP, Blessing JA, DiSaia PJ, McGuire WP; Gynecologic Oncology Group. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. [https://doi.org/10.1006/gyno.1993.1084 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8482560/ PubMed]
+==Paclitaxel monotherapy {{#subobject:635f43|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 135 mg/m<sup>2</sup> {{#subobject:723bf0|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.1996.14.3.792 McGuire et al. 1996]
+|1990
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001]
+|1994
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+''Note: this was the dosage used for patients with previous pelvic radiation.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*[[Paclitaxel (Taxol)]] dose could be changed to 110 or 200 mg/m<sup>2</sup> depending on toxicity
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 170 mg/m<sup>2</sup> {{#subobject:6eac87|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.1996.14.3.792 McGuire et al. 1996]
+|1990
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001]
+|1994
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] by the following exposure-based criteria:
+**No previous pelvic radiation: 170 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+**Previous pelvic radiation: 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*[[Paclitaxel (Taxol)]] dose could be changed to 110 or 200 mg/m<sup>2</sup> depending on toxicity
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 250 mg/m<sup>2</sup> {{#subobject:4c3e15|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]]
+|-
+|[http://clincancerres.aacrjournals.org/content/2/8/1285.long Kudelka et al. 1996]
+|NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 20 mg PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 60 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 60 minutes prior to paclitaxel
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 2, 24 hours after paclitaxel, given until day 19 or until ANC greater or equal to 10,000/μL
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*[[Paclitaxel (Taxol)]] dose could be changed to 275, 225, or 200 mg/m<sup>2</sup> depending on toxicity
+</div></div>
+===References===
+# McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G; Gynecologic Oncology Group. Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [https://doi.org/10.1200/jco.1996.14.3.792 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8622025/ PubMed]
+# Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. [http://clincancerres.aacrjournals.org/content/2/8/1285.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9816298/ PubMed] content property of [https://hemonc.org HemOnc.org]
+## '''Update:''' Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. [https://doi.org/10.1097/00001813-199708000-00002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9311440/ PubMed]
+# Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD; Gynecologic Oncology Group. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [https://doi.org/10.1200/jco.2001.19.5.1275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11230468/ PubMed]
+==Paclitaxel & Topotecan {{#subobject:PYR2|Regimen=1}}==
+TP: '''<u>T</u>'''opotecan, '''<u>P</u>'''aclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:PYV2|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=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)]
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|2. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br>
+''Note: per the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''21-day cycles'''
+</div></div>
+===References===
+# '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062]
+## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed]
+## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed]
+==Paclitaxel, Topotecan, Bevacizumab {{#subobject:PYR3|Regimen=1}}==
+TP+Bev: '''<u>T</u>'''opotecan, '''<u>P</u>'''aclitaxel, '''<u>Bev</u>'''acizumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:PYV3|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=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|rowspan=3|2009-2012
+|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|2. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|3. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br>
+''Note: in the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV once per day on days 1 to 3
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/21/4626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15911865 PubMed]
+# '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062]
-# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed]
+## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed]
-==Cisplatin & Vinorelbine {{#subobject:176775|Regimen=1}}==
+==Topotecan monotherapy {{#subobject:720120|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, q3wk {{#subobject:be1724|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.2000.5807 Bookman et al. 2000 (GOG 127-F)]
+|1994-12 to NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<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><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, q4wk {{#subobject:469fbe|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.2000.6024 Muderspach et al. 2001 (GOG 76-U)]
+|1994-01 to 1995-12
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:e442f7|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-{| border="1" style="text-align:center;" !align="left"
+====Chemotherapy====
-|'''Study'''
+*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+'''28-day cycles'''
-|'''Comparator'''
+</div></div>
+===References===
+# Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA; Gynecologic Oncology Group. Topotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [https://doi.org/10.1006/gyno.2000.5807 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10831357/ PubMed]
+# '''GOG 76-U:''' Muderspach LI, Blessing JA, Levenback C, Moore JL Jr; Gynecologic Oncology Group. A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Gxroup study. Gynecol Oncol. 2001 May;81(2):213-5. [https://doi.org/10.1006/gyno.2000.6024 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11354055/ PubMed]
+==Vinorelbine monotherapy {{#subobject:b92b24|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e1af3|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]]
 |-
-|[http://jco.ascopubs.org/content/27/28/4649.long Monk et al. 2009]
+|[https://doi.org/10.1200/jco.1998.16.3.1094 Morris et al. 1998]
-|<span
+|1993-1995
-style="background:#00CD00;
+|style="background-color:#91cf61"|Phase 2
-padding:3px 6px 3px 6px;
+|ORR: 18%
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Cervical_cancer#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]<br> [[Cervical_cancer#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br> [[Cervical_cancer#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]]
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1
+====Chemotherapy====
-*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV once per day on days 1 & 8
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1
+'''7-day cycles'''
-'''21-day cycles; if not responding, given for maximum of 6 cycles'''
+</div></div>
 ===References===
-# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+# Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [https://doi.org/10.1200/jco.1998.16.3.1094 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9508195/ PubMed]
+=Advanced or metastatic disease, subsequent lines of therapy=
-==Docetaxel (Taxotere) {{#subobject:95153c|Regimen=1}}==
+==Bevacizumab monotherapy {{#subobject:1da8f9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:67b93c|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/PMC2667811/ Monk et al. 2009 (GOG 227-C)]
+|2002-2006
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
-===Regimen #1, Garcia et al. 2007 {{#subobject:744f01|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Targeted therapy====
-<span
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Docetaxel (Taxotere)]] 100 mg/m2 IV over 1 hour on day 1
 '''21-day cycles'''
+</div></div>
+===References===
+<!-- Presented in part at the 39th Annual Meeting of the Society of Gynecologic Oncologists, March 9-12, 2008, Tampa, FL. -->
+# Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD; Gynecologic Oncology Group. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. [https://doi.org/10.1200/jco.2008.18.9043 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667811/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19139430/ PubMed]
+==Cemiplimab monotherapy {{#subobject:1dhg19|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:684026|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/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-361-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|1a. [[#Pemetrexed_monotherapy|Pemetrexed]]<br>1b. [[#Topotecan_monotherapy_2|Topotecan]]<br>1c. [[#Irinotecan_monotherapy|Irinotecan]]<br>1d. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1e. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 12 vs 8.5 mo<br>(HR 0.69, 95% CI 0.56-0.84)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Cemiplimab (Libtayo)]] 350 mg IV once on day 1
+'''21-day cycle for up to 32 cycles (96 weeks)'''
+</div></div>
+===References===
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
-===Regimen #2, Garcia et al. 2008 {{#subobject:328695|Variant=1}}===
+==Cisplatin & Gemcitabine (GC) {{#subobject:d9cdf3|Regimen=1}}==
-Level of Evidence:
+GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin
-<span
+<div class="toccolours" style="background-color:#eeeeee">
-style="background:#EEEE00;
+===Regimen {{#subobject:684026|Variant=1}}===
-padding:3px 6px 3px 6px;
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-border-color:black;
+!style="width: 33%"|Study
-border-width:2px;
+!style="width: 33%"|Dates of enrollment
-border-style:solid;">Phase II</span>
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
-*[[Docetaxel (Taxotere)]] 36 mg/m2 IV over 1 hour on days 1, 8, 15
+|[https://doi.org/10.1016/j.ygyno.2005.09.009 Brewer et al. 2006]
+|2001-2002
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once on day 1, '''given first'''
+*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second'''
 '''28-day cycles'''
+</div></div>
-Supportive medications:
+===References===
+# Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL; Gynecologic Oncology Group. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. [https://doi.org/10.1016/j.ygyno.2005.09.009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16271750/ PubMed]
+==Docetaxel monotherapy {{#subobject:95153c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 36 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:328695|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.2008.06.013 Garcia et al. 2008]
+|2004-07 to 2005-04
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 36 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+====Supportive therapy====
 *[[Dexamethasone (Decadron)]] 8 mg PO the evening before, morning of, and evening of each dose of docetaxel
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 100 mg/m<sup>2</sup>, q3wk {{#subobject:744f01|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]]
+|-
+|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2007&issue=08000&article=00014&type=abstract Garcia et al. 2007]
+|2002-06 to 2004-12
+|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
+'''21-day cycles'''
+</div></div>
 ===References===
-# Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group Study. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Am J Clin Oncol. 2007 Aug;30(4):428-31. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2007&issue=08000&article=00014&type=abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17762444 PubMed]
+# Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 2007 Aug;30(4):428-31. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2007&issue=08000&article=00014&type=abstract link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17762444/ PubMed]
-# Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. [http://www.sciencedirect.com/science/article/pii/S0090825808004526 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18675446 PubMed]
+# Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. [https://doi.org/10.1016/j.ygyno.2008.06.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18675446/ PubMed]
+==FULV {{#subobject:e38061|Regimen=1}}==
-==Fluorouracil & Folinic acid {{#subobject:e38061|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 1850/200 {{#subobject:937680|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://journals.lww.com/amjclinicaloncology/Fulltext/1996/10000/A_Phase_II_Trial_of_5_Fluorouracil_and_High_Dose.2.aspx Look et al. 1996]
+|1990-1992
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1006/gyno.1997.4886 Look et al. 1997]
+|1993-1995
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+''Note: it is not entirely clear from these publications whether leucovorin is given on day 1 only, versus on days 1 to 5.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 5, '''given second'''
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV bolus once on day 1 (see note), '''given first'''
+'''28-day cycle for 2 cycles, then 35-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 2125/100 {{#subobject:c76c92|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/10.1097/00000421-199212000-00007 Look et al. 1992]
+|1989-09 to 1990-04
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
-===Regimen #1, Look et al. 1996 & Look et al. 1997 {{#subobject:937680|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
-style="background:#EEEE00;
+*[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given first'''
-padding:3px 6px 3px 6px;
+'''28-day cycle for 2 cycles, then 35-day cycles'''
-border-color:black;
+</div></div>
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Folinic acid (Leucovorin)]] 200 mg/m2 IV bolus on days 1 to 5, given first
-*[[Fluorouracil (5-FU)]] 370 mg/m2 IV bolus over 5 minutes once per day on days 1 to 5, given second
-'''28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity'''
-===Regimen #2, Look et al. 1992 {{#subobject:c76c92|Variant=1}}===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV once per day on days 1 to 5, given first
-*[[Fluorouracil (5-FU)]] 425 mg/m2 IV once per day on days 1 to 5, given second
-'''28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity'''
 ===References===
-# Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. [http://www.ncbi.nlm.nih.gov/pubmed/1449112 PubMed]
+# Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH; Gynecologic Oncology Group. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. [https://doi.org/10.1097/00000421-199212000-00007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1449112/ PubMed]
-# Look KY, Blessing JA, Gallup DG, Lentz SS. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. [http://www.ncbi.nlm.nih.gov/pubmed/8823469 PubMed]
+# Look KY, Blessing JA, Gallup DG, Lentz SS; Gynecologic Oncology Group. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. [https://journals.lww.com/amjclinicaloncology/Fulltext/1996/10000/A_Phase_II_Trial_of_5_Fluorouracil_and_High_Dose.2.aspx link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8823469/ PubMed]
-# Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. [http://www.sciencedirect.com/science/article/pii/S0090825897948861 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9441772 PubMed]
+# Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA; Gynecologic Oncology Group. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. [https://doi.org/10.1006/gyno.1997.4886 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9441772/ PubMed]
+==Gemcitabine monotherapy {{#subobject:313d78|Regimen=1}}==
-==Gemcitabine (Gemzar) {{#subobject:313d78|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen variant #1 {{#subobject:9f6038|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.1999.5671 Schilder et al. 2000 (GOG 127-K)]
+|NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1016/j.ygyno.2004.09.027 Schilder et al. 2005]
+|NR
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:9f6038|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Chemotherapy====
-<span
+*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Gemcitabine (Gemzar)]] 800 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
 '''28-day cycles'''
+</div></div><br>
-===References===
+<div class="toccolours" style="background-color:#eeeeee">
-# Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group. Gynecol Oncol. 2000 Feb;76(2):204-7. [http://www.sciencedirect.com/science/article/pii/S0090825899956718 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10637071 PubMed]
+===Regimen variant #2 {{#subobject:7tyg1h|Variant=1}}===
-# Schilder RJ, Blessing J, Cohn DE. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. [http://www.sciencedirect.com/science/article/pii/S0090825804007735 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15589587 PubMed]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
-==Ifosfamide (Ifex) {{#subobject:1d18ed|Regimen=1}}==
+!style="width: 20%"|Dates of enrollment
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!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/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cemiplimab_monotherapy|Cemiplimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:962339|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV once per day on days 1 to 5
-**Dosage for patients with previous pelvic radiation or other chemotherapy is [[Ifosfamide (Ifex)]] 1200 mg/m2
-**Dose of [[Ifosfamide (Ifex)]] could be increased by 300 mg/m2 or decreased by 20% depending on toxicity
-*[[Mesna (Mesnex)]] at 20% of ifosfamide dose (for example, 300 mg/m2 for 1500 mg/m2 dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5
 '''21-day cycles'''
+</div></div>
 ===References===
-# Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. [http://www.ncbi.nlm.nih.gov/pubmed/3802384 PubMed]
+# '''GOG 127-K:''' Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS; Gynecologic Oncology Group. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Feb;76(2):204-7. [https://doi.org/10.1006/gyno.1999.5671 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10637071/ PubMed]
-# Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. [http://www.ncbi.nlm.nih.gov/pubmed/8456884 PubMed]
+# Schilder RJ, Blessing J, Cohn DE; Gynecologic Oncology Group. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. [https://doi.org/10.1016/j.ygyno.2004.09.027 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15589587/ PubMed]
-# Sutton GP, Blessing JA, DiSaia PJ, McGuire WP. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. [http://www.sciencedirect.com/science/article/pii/S009082588371084X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8482560 PubMed]
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
-==Irinotecan (Camptosar) {{#subobject:e80134|Regimen=1}}==
+==Irinotecan monotherapy {{#subobject:e80134|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1 {{#subobject:91yugf|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/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cemiplimab_monotherapy|Cemiplimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+'''42-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2 {{#subobject:fe2b8e|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.1997.15.2.625 Verschraegen et al. 1997]
+|1993-1995
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:fe2b8e|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
-padding:3px 6px 3px 6px;
+====Supportive therapy====
-border-color:black;
+*[[Diphenhydramine (Benadryl)]] 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion
-border-width:2px;
+*[[Atropine (Atropen)]] 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
-border-style:solid;">Phase II</span>
+*[[Loperamide (Imodium)]] 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions
-*[[Irinotecan (Camptosar)]] 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
 '''42-day cycles'''
+</div></div>
-Supportive medications:
+===References===
-*Diphenhydramine (Benadryl) 25-50 mg PO/IV every 6 hours as needed for diarrhea during irinotecan infusion
+# Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. [https://doi.org/10.1200/jco.1997.15.2.625 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9053486/ PubMed]
-*Atropine 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
-*Loperamide 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
+==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7b36e9|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable" 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.18.01265 Chung et al. 2019 (KEYNOTE-158<sub>cervical</sub>)]
+|2016-01-27 to 2016-08-18
+|style="background-color:#91cf61"|Phase 2 (RT)
+|-
+|}
+''Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
 ===References===
-# Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. [http://jco.ascopubs.org/content/15/2/625.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9053486 PubMed]
+<!-- # '''Abstract:''' Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. [https://doi.org/10.1200/JCO.2017.35.15_suppl.5514 link to abstract] -->
+# '''KEYNOTE-158<sub>cervical</sub>:''' Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Epub 2019 Apr 3. [https://doi.org/10.1200/JCO.18.01265 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30943124/ PubMed] [https://clinicaltrials.gov/study/NCT02628067 NCT02628067]
-==Paclitaxel (Taxol) {{#subobject:635f43|Regimen=1}}==
+==Pemetrexed monotherapy {{#subobject:57456b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1 {{#subobject:gh4w1h|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/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cemiplimab_monotherapy|Cemiplimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen #1, Kudelka et al. 1996 & Kudelka et al. 1997 {{#subobject:4c3e15|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Paclitaxel (Taxol)]] 250 mg/m2 IV over 3 hours on day 1
-**Dose of [[Paclitaxel (Taxol)]] could be changed to 275, 225, or 200 mg/m2 depending on toxicity
 '''21-day cycles'''
+</div></div><br>
-Supportive medications:
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Dexamethasone (Decadron)]] 20 mg PO 14 and 7 hours prior to paclitaxel
+===Regimen variant #2 {{#subobject:db8999|Variant=1}}===
-*Cimetidine (Tagamet) 300 mg IV 60 minutes prior to paclitaxel
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-*Diphenhydramine (Benadryl) 50 mg IV 60 minutes prior to paclitaxel
+!style="width: 33%"|Study
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily starting on day 2, 24 hours after chemotherapy, given until day 19 or until ANC greater or equal to 10,000
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-===Regimen #2, McGuire et al. 1996 & Curtin et al. 2001 {{#subobject:6eac87|Variant=1}}===
+|-
-Level of Evidence:
+|[https://doi.org/10.1016/j.ygyno.2008.03.009 Miller et al. 2008]
-<span
+|2004-2006
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Phase 2
-padding:3px 6px 3px 6px;
+|-
-border-color:black;
+|}
-border-width:2px;
+<div class="toccolours" style="background-color:#b3e2cd">
-border-style:solid;">Phase II</span>
+====Chemotherapy====
+*[[Pemetrexed (Alimta)]] 900 mg/m<sup>2</sup> IV over 10 minutes once on day 1
-*[[Paclitaxel (Taxol)]] 170 mg/m2 IV continuous infusion over 24 hours on day 1
+====Supportive therapy====
-**Dosage for patients with previous pelvic radiation was [[Paclitaxel (Taxol)]] 135 mg/m2
+*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
-**Dose of [[Paclitaxel (Taxol)]] could be changed to 110 or 200 mg/m2 depending on toxicity
+*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM 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>
-Supportive medications:
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV 14 and 7 hours prior to paclitaxel
-*Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
-*Ranitidine (Zantac) 50 mg IV 30 minutes prior to paclitaxel
 ===References===
-# McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [http://jco.ascopubs.org/content/14/3/792.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8622025 PubMed]
+# Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. [https://doi.org/10.1016/j.ygyno.2008.03.009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18455781/ PubMed]
-# Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. [http://clincancerres.aacrjournals.org/content/2/8/1285.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9816298 PubMed] content property of [http://hemonc.org HemOnc.org]
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
-# '''Update:''' Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. [http://www.ncbi.nlm.nih.gov/pubmed/9311440 PubMed]
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
-# Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [http://jco.ascopubs.org/content/19/5/1275.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11230468 PubMed]
+==Tisotumab vedotin monotherapy {{#subobject:2sbn6b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Pemetrexed (Alimta) {{#subobject:57456b|Regimen=1}}==
+===Regimen {{#subobject:ghg72h|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable" 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]]
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00056-5 Coleman et al. 2021 (innovaTV 204)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-299-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+|-
+|} -->
+|2018-06-12 to 2019-04-11
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
+|1a. [[#Pemetrexed_monotherapy|Pemetrexed]]<br>1b. [[#Topotecan_monotherapy_2|Topotecan]]<br>1c. [[#Irinotecan_monotherapy|Irinotecan]]<br>1d. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1e. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 11.5 vs 9.5 mo<br>(HR 0.70, 95% CI 0.54-0.89)
 |-
-|[[#toc|back to top]]
 |}
-===Regimen {{#subobject:db8999|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-Level of Evidence:
+====Antibody-drug conjugate therapy====
-<span
+*[[Tisotumab vedotin (Tivdak)]] 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Pemetrexed (Alimta)]] 900 mg/m2 IV over 10 minutes on day 1
 '''21-day cycles'''
+</div></div>
-Supportive medications:
-*Folic acid 350-600 mcg PO daily, 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 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
 ===References===
-# Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. [http://www.sciencedirect.com/science/article/pii/S0090825808002035 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18455781 PubMed]
+#'''innovaTV 204:''' Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. Epub 2021 Apr 9. [https://doi.org/10.1016/s1470-2045(21)00056-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33845034/ PubMed] [https://clinicaltrials.gov/study/NCT03438396 NCT03438396]
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
-==Topotecan (Hycamtin) {{#subobject:720120|Regimen=1}}==
+==Topotecan monotherapy {{#subobject:218ug1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1 {{#subobject:91yg1h|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/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cemiplimab_monotherapy|Cemiplimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen #1, Bookman et al. 2000 {{#subobject:be1724|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV once per day on days 1 to 5
-padding:3px 6px 3px 6px;
+'''21-day cycles'''
-border-color:black;
+</div></div><br>
-border-width:2px;
+<div class="toccolours" style="background-color:#eeeeee">
-border-style:solid;">Phase II</span>
+===Regimen variant #2 {{#subobject:7tyg1h|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
+!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.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Dosing information is from CT.gov.''
+<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
 '''21-day cycles'''
+</div></div>
-===Regimen #2, Muderspach et al. 2001 {{#subobject:469fbe|Variant=1}}===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
-'''28-day cycles'''
 ===References===
-# Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [http://www.sciencedirect.com/science/article/pii/S0090825800958074 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10831357 PubMed]
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
-# Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol. 2001 May;81(2):213-5. [http://www.sciencedirect.com/science/article/pii/S0090825800960244 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11354055 PubMed]
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
+==Vinorelbine monotherapy {{#subobject:2186af|Regimen=1}}==
-==Vinorelbine (Navelbine) {{#subobject:b92b24|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:ba6a7e|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.2003.10.045 Muggia et al. 2004]
+|1997-1999
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+|ORR: 14% (95% CI 5-27%)
+|-
+|[https://doi.org/10.1016/j.ygyno.2004.09.028 Muggia et al. 2005]
+|1997-1999
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+|ORR: 7%
+|-
+|[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cemiplimab_monotherapy|Cemiplimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)]
+|2021-2023
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]]
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#toc|back to top]]
 |}
-===Regimen #1, Muggia et al. 2004 & Muggia et al. 2005 {{#subobject:ba6a7e|Variant=1}}===
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-Level of Evidence:
+<div class="toccolours" style="background-color:#b3e2cd">
-<span
+====Chemotherapy====
-style="background:#EEEE00;
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
-===Regimen #2, Morris et al. 1998 {{#subobject:e1af3|Variant=1}}===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV on day 1
-'''7-day cycles'''
 ===References===
-# Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [http://jco.ascopubs.org/content/16/3/1094.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9508195 PubMed]
+# Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. [https://doi.org/10.1016/j.ygyno.2003.10.045 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14766259/ PubMed]
-# Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group study. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. [http://www.sciencedirect.com/science/article/pii/S0090825803007704 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14766259 PubMed]
+# Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Jan;96(1):108-11. [https://doi.org/10.1016/j.ygyno.2004.09.028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15589588/ PubMed]
-# Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group Study. Gynecol Oncol. 2005 Jan;96(1):108-11. [http://www.sciencedirect.com/science/article/pii/S0090825804007747 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15589588 PubMed]
+#'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267]
+#'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628]
+[[Category:Cervical cancer regimens]]
+[[Category:Disease-specific pages]]
+[[Category:Gynecologic cancers]]

Difference between revisions of "Cervical cancer"

Revision as of 19:29, 23 June 2024

Guidelines

ASCO

ESMO

NCCN

Neoadjuvant chemotherapy

Cisplatin & Paclitaxel

Regimen

Chemotherapy

Supportive therapy

Subsequent treatment

References

Definitive therapy for locally advanced disease

Brachytherapy protocol

Regimen

Radiotherapy

References

Carboplatin & RT

Regimen variant #1, AUC-based carboplatin

Chemotherapy

Radiotherapy

Subsequent treatment

Regimen variant #2, BSA-based carboplatin

Chemotherapy

Radiotherapy

References

Cisplatin & RT

Regimen variant #1, weekly cisplatin x 5, no cap + 4500 cGy

Chemotherapy

Radiotherapy

Subsequent treatment

Regimen variant #2, weekly cisplatin x 5, no cap + 5000 cGy

Chemotherapy

Supportive therapy

Radiotherapy

Subsequent treatment

Regimen variant #3, weekly cisplatin x 6, no cap

Chemotherapy

Radiotherapy

Subsequent treatment

Regimen variant #4, weekly cisplatin x 6, capped

Chemotherapy

Radiotherapy

Subsequent treatment

Regimen variant #5, q3wk cisplatin x 3

Chemotherapy

Radiotherapy

Subsequent treatment

References

Cisplatin, Pembrolizumab, RT

Regimen

Chemotherapy

Radiotherapy

Immunotherapy

References

Cisplatin & Fluorouracil (CF) & RT

Regimen variant #1, 70/4000 x 4

Chemotherapy

Radiotherapy

Regimen variant #2, 75/4000 x 3

Chemotherapy

Radiotherapy

Subsequent treatment

References

Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT

Definitive therapy

Chemotherapy

Radiotherapy

Consolidation

Radiotherapy

References

Cisplatin & Gemcitabine (GC) & RT

Regimen

Chemotherapy

Radiotherapy

Subsequent treatment

References

Fluorouracil & RT

Definitive therapy