Cervical cancer
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48 regimens on this page
66 variants on this page
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Guidelines
ASCO
Older
- 2016: Chuang et al. Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline
ESMO
- 2017: Marth et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 2012: Colombo et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Neoadjuvant chemotherapy
Cisplatin & Paclitaxel
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Park et al. 2004 | NR in abstract | 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 medications
- Dexamethasone (Decadron) 20 mg PO twice on day 1; 12 and 6 hours prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- 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 verified protocol PubMed
Definitive chemoradiotherapy for locally advanced disease
Carboplatin & RT
Carboplatin & RT: Carboplatin & Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Veerasarn et al. 2006 | 2001-2003 | Phase 3 (C) | Carboplatin, UFT, RT | Did not meet primary endpoints of TTP/OS |
Chemotherapy
- Carboplatin (Paraplatin) 100 mg/m2 IV over 30 to 60 minutes once on day 1
7-day cycle for 5 to 6 cycles, according to RT duration
Radiotherapy
- Concurrent radiation therapy
One 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 verified protocol PubMed
- CALLA: NCT03830866
Cisplatin & RT
Cisplatin & RT: Cisplatin & Radiation Therapy
Regimen variant #1, weekly cisplatin x 5, no cap
Study | Years 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 |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV once on day 1
Supportive medications
- Ondansetron (Zofran) 16 mg (route not specified) once on day 1, prior to Cisplatin (Platinol)
- Dexamethasone (Decadron) 8 mg (route not specified) once on day 1, prior to Cisplatin (Platinol)
- Pre- and post- cisplatin hydration
7-day cycle for 5 cycles
Radiotherapy, part 1
- Concurrent radiation therapy: 2 Gy x 25 fractions, for a dose of 50 Gy
5-week course, followed by:
Radiotherapy, part 2
- See paper for details
Regimen variant #2, weekly cisplatin x 6, no cap
Study | Years 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 primary endpoints of PFS/OS |
2. Hydroxyurea & RT | Superior OS | |||
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 (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 |
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, part 1
- Concurrent radiation therapy by the following study-specific criteria:
- GOG 120, stage IIB: 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
- GOG 219: Concurrent radiation therapy: 1.8 Gy x 23 to 25 fractions, for an initial dose of 41.4 to 45 Gy
- Pearcey et al. 2002 & Zuliani et al. 2014: 1.8 Gy x 25 fractions, for an initial dose of 45 Gy
- B9E-MC-JHQS & Sehouli et al. 2012: 1.8 Gy x 28 fractions, for an initial dose of 50.4 Gy
- GOG 120, stage III or IVA: 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
6-week course, followed in 1 to 3 weeks by:
Radiotherapy, part 2
- 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: 30 Gy for a total dose of 81 Gy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
- B9E-MC-JHQS & Sehouli et al. 2012: 30 to 35 Gy delivered to point A
- GOG 219: 35 to 43.6 Gy to point A
- GOG 120, stage IIB: 40 Gy for a total dose of 80.8 Gy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
Regimen variant #3, weekly cisplatin x 6, capped
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Keys et al. 1999 (GOG 123) | 1992-1997 | Phase 3 (E-esc) | RT | Superior OS |
Lanciano et al. 2005 (GOG 165) | 1997-2000 | Phase 3 (E-switch-ic) | Fluorouracil & RT | Might have superior ORR |
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, part 1
- Concurrent radiation therapy: 1.8 Gy x 25 fractions, for an initial dose of 45 Gy
6-week course, followed by:
Radiotherapy, part 2
- Brachytherapy by the following study-specific criteria:
- GOG 123: 30 Gy to point A for a total dose of 75 Gy
- GOG 165: ONE of the following:
- Low-dose rate intracavitary brachytherapy of 40 Gy to point A given in 1 to 2 fractions
- High-dose rate intracavitary brachytherapy of 30 Gy to point A given in 5 fractions, starting week 4 of XRT
- GOG 165: Parametrial boost of 5.4 to 9 Gy was administered to the involved parametrium after whole pelvic RT was complete
Subsequent treatment
- GOG 123: Adjuvant hysterectomy
Regimen variant #4, q3wk cisplatin x 3
Study | Years 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 on day 1
21-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy: 1.8 to 2 Gy, for an initial dose of 50 Gy
- Brachytherapy, see paper for details
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 verified protocol 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. 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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol 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
- 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 protocol 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 verified protocol in supplement PubMed NCT00193791
- CALLA: NCT03830866
Cisplatin & Fluorouracil (CF) & RT
CF & RT: Cisplatin, Fluorouracil Radiation Therapy
Regimen variant #1, 70/4000 x 4
Study | Years 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 |
Peters et al. 2000 (GOG 109/SWOG-8797) | 1991-1996 | Phase 3 (E-esc) | Radiation therapy | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 4000 mg/m2)
21-day cycle for 4 cycles
Radiotherapy
- Concurrent radiation therapy: 1.7 Gy x 29 fractions, for a total dose of 49.3 Gy, starting on cycle 1 day 1
- Patients with positive high common iliac lymph nodes also received 1.5 Gy x 30 fractions, for a total dose of 45 Gy
6-week course
Regimen variant #2, 75/4000 x 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morris et al. 1999 | 1990-1997 | Phase 3 (E-esc) | Radiation therapy | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 4 hours once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 4000 mg/m2)
21-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy: 1.8 Gy x 25 fractions, for a total dose of 45 Gy, starting on cycle 1 day 0 or 1
5-week course
Subsequent treatment
- Brachytherapy (see paper for details)
References
- 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 verified protocol 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 verified protocol PubMed
Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT
Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rose et al. 1999 (GOG 120) | 1992-1997 | Phase 3 (E-esc) | 1. Cisplatin & RT | Did not meet primary endpoints of PFS/OS |
2. Hydroxyurea & RT | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (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
28-day cycle for 2 cycles
Radiotherapy, part 1
- Concurrent radiation therapy by the following criteria:
- Stage IIB: 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
- Stage III or IVA: 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
5- to 6-week course, followed by:
Radiotherapy, part 2
- Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
- Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
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 verified protocol 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. link to original article PubMed
Cisplatin & Gemcitabine (GC) & RT
Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, Radiation Therapy
Regimen
Study | Years 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 OS Median OS: NYR vs NYR (HR 0.68, 95% CI 0.49-0.95) |
Cetina et al. 2013 | 2004-2009 | Non-randomized portion of 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: 1.8 Gy x 28 fractions, for an initial dose of 50.4 Gy
6-week course
Subsequent treatment
- B9E-MC-JHQS: Brachytherapy (30 to 35 Gy delivered to point A), then adjuvant cisplatin & gemcitabine, 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 verified protocol 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 protocol PubMed
Fluorouracil & RT
5-FU & RT: 5-FluouroUracil & Radiation Therapy
Regimen
Study | Years 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 |
Chemotherapy
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 1125 mg/m2)
7-day cycle for 6 cycles
Radiotherapy, part 1
- Concurrent radiation therapy, 1.8 Gy x 25 fractions, for an initial dose of 40.8 Gy
6-week course, followed by:
Radiotherapy, part 2
- 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 to 9 Gy 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 verified protocol PubMed NCT00003078
Fluorouracil, Mitomycin, RT
Fluorouracil, Mitomycin, RT: Fluorouracil, Mitomycin, Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lorvidhava et al. 2003 | 1988-1994 | Phase 3 (E-esc) | RT | Superior DFS |
Here for historic reference.
Chemotherapy
Radiotherapy
- Concurrent radiation therapy
References
- Lorvidhaya V, Chitapanarux I, Sangruchi S, Lertsanguansinchai P, Kongthanarat Y, Tangkaratt S, Visetsiri E. Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1226-32. link to original article PubMed
Hydroxyurea & RT
Hydroxyurea & RT: Hydroxyurea & Radiation Therapy
Regimen
Study | Years 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 |
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 |
2. Cisplatin, Fluorouracil, Hydroxyurea, RT | Inferior OS |
Chemotherapy
- Hydroxyurea (Hydrea) 2000 mg/m2 PO two times per week, given 2 hours before radiation on weeks 1 to 6
Radiotherapy, part 1
- Concurrent radiation therapy by the following criteria:
- Stage IIB: 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
- Stage III or IVA: 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
6-week course, followed in 1 to 3 weeks by:
Radiotherapy, part 2
- Intracavitary brachytherapy by the following criteria:
- Stage IIB: 40 Gy for a total dose of 80.8 Gy to point A
- Stage III or IVA: 30 Gy for a total dose of 81 Gy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
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 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 verified protocol 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. 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
Radiation therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hreshchyshyn et al. 1979 (GOG 04) | 1970-1976 | Phase 3 (C) | Hydroxyurea & RT | Seems to have inferior OS |
Benedetti-Panici et al. 2002 | 1990-1996 | Phase 3 (C) | NACT, then surgery | Inferior OS |
Morris et al. 1999 | 1990-1997 | Phase 3 (C) | Cisplatin & RT | Inferior OS |
Peters et al. 2000 (GOG 109/SWOG-8797) | 1991-1996 | Phase 3 (C) | Cisplatin, Fluorouracil, RT | Inferior OS |
Pearcey et al. 2002 | 1991-1996 | Phase 3 (C) | Cisplatin & RT | Did not meet primary endpoint of OS36 |
Keys et al. 1999 (GOG 123) | 1992-1997 | Phase 3 (C) | Cisplatin & RT | Inferior OS |
Shrivastava et al. 2018 (CRACx) | 2003-2011 | Phase 3 (C) | Cisplatin & RT | Seems to have inferior OS |
Sugiyama et al. 2014 (JGOG-DT101) | 2004-2006 | Phase 3 (C) | Z-100 & RT | Did not meet primary endpoint of OS |
Srivastava et al. 2013 | 2006-2008 | Phase 3 (C) | Cisplatin & RT | Did not meet primary endpoint of LRFS |
Huang et al. 2021 (STARS) | 2008-2018 | Phase 3 (C) | 1. Cisplatin & RT | Did not meet primary endpoint of DFS |
2. Cisplatin & Paclitaxel x2, then RT, then Cisplatin & Paclitaxel x2 | Seems to have inferior OS |
Demonstrably inferior; here for reference purposes only.
Radiotherapy
Subsequent treatment
- Hreshchyshyn et al. 1979 & GOG 123: adjuvant hysterectomy
References
- GOG 04: 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
- DiSaia PJ, Bundy BN, Curry SL, Schlaerth J, Thigpen JT. Phase III study on the treatment of women with cervical cancer, stage IIB, IIIB, and IVA (confined to the pelvis and/or periaortic nodes), with radiotherapy alone versus radiotherapy plus immunotherapy with intravenous Corynebacterium parvum: a Gynecologic Oncology Group Study. Gynecol Oncol. 1987 Mar;26(3):386-97. link to original article PubMed
- 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 verified protocol 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 verified protocol 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 verified protocol PubMed
- Benedetti-Panici P, Greggi S, Colombo A, Amoroso M, Smaniotto D, Giannarelli D, Amunni G, Raspagliesi F, Zola P, Mangioni C, Landoni F. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. J Clin Oncol. 2002 Jan 1;20(1):179-88. link to original article PubMed
- 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 verified protocol PubMed
- Srivastava K, Paul S, Chufal KS, Shamsundar SD, Lal P, Pant MC, Bhatt M, Singh S, Gupta R. Concurrent chemoradiation versus radiotherapy alone in cervical carcinoma: a randomized phase III trial. Asia Pac J Clin Oncol. 2013 Dec;9(4):349-56. Epub 2013 May 27. link to original article PubMed
- JGOG-DT101: Sugiyama T, Fujiwara K, Ohashi Y, Yokota H, Hatae M, Ohno T, Nagai Y, Mitsuhashi N, Ochiai K, Noda K. Phase III placebo-controlled double-blind randomized trial of radiotherapy for stage IIB-IVA cervical cancer with or without immunomodulator Z-100: a JGOG study. Ann Oncol. 2014 May;25(5):1011-7. Epub 2014 Feb 25. link to original article PubMed UMIN C000000221
- 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 verified protocol in supplement PubMed NCT00193791
- STARS: Huang H, Feng YL, Wan T, Zhang YN, Cao XP, Huang YW, Xiong Y, Huang X, Zheng M, Li YF, Li JD, Chen GD, Li H, Chen YL, Ma LG, Yang HY, Li L, Yao SZ, Ye WJ, Tu H, Huang QD, Liang LZ, Liu FY, Liu Q, Liu JH. Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Mar 1;7(3):361-369. link to original article link to PMC article PubMed NCT00806117
Adjuvant therapy
Carboplatin & Ifosfamide
Regimen
Study | Years 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 prior to becoming a standard comparator arm.
Preceding treatment
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
Supportive medications
- Mesna (Mesnex) 1600 mg/m2 IV over 6 hours once per day on days 1 to 3, with Ifosfamide (Ifex)
21-day cycle for 4 cycles
Subsequent treatment
- Pelvic EBRT x 50.4 Gy
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 verified protocol PubMed
Cisplatin & Gemcitabine (GC)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Dueñas-González et al. 2011 (B9E-MC-JHQS) | 2002-2004 | Non-randomized portion of RCT |
Preceding treatment
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 verified protocol PubMed NCT00191100
Radiation therapy
Regimen
Study | Years 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 Carboplatin & Ifosfamide x 4
Radiotherapy
- External beam radiotherapy: 1.8 Gy for 28 fractions, for a total dose of 50.4 Gy
- If resection margins positive, patients received one of the following:
- EBRT boost of 2 x 5 Gy
- 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 verified protocol PubMed
Persistent, recurrent, or metastatic disease, first-line therapy
Carboplatin monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Weiss et al. 1990 | NR in abstract | 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 PubMed
Carboplatin & Docetaxel
Regimen variant #1, 6 cycles
Study | Years of enrollment | Evidence |
---|---|---|
Takekida et al. 2010 | NR in abstract | 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 medications
- 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 | Years of enrollment | Evidence |
---|---|---|
Nagao et al. 2005 | 2001-2004 | Pilot, <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 medications
- 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 verified protocol 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 | Years 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 |
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1. CP & Pembrolizumab 2. CP, Bevacizumab, Pembrolizumab 3. Cisplatin, Paclitaxel, Pembrolizumab 4. 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 protocol 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 verified protocol 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 verified protocol PubMed NCT03635567
Carboplatin & Paclitaxel (CP) & Bevacizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1. CP & Pembrolizumab 2. CP, Bevacizumab, Pembrolizumab 3. Cisplatin, Paclitaxel, Pembrolizumab 4. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
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. 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 verified protocol PubMed NCT03635567
Carboplatin & Paclitaxel (CP), Bevacizumab, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1. CP 2. CP & Bevacizumab 3. Cisplatin & Paclitaxel 4. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 OS24: 50.4% vs 40.4% (HR 0.67, 95% CI 0.54-0.84) |
1Reported efficacy is for the ITT population
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 verified protocol PubMed NCT03635567
Carboplatin & Paclitaxel (CP) & Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1. CP 2. CP & Bevacizumab 3. Cisplatin & Paclitaxel 4. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 OS24: 50.4% vs 40.4% (HR 0.67, 95% CI 0.54-0.84) |
1Reported efficacy is for the ITT population
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 verified protocol PubMed NCT03635567
Cisplatin monotherapy
Regimen
Study | Years 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) | Cisplatin & Ifosfamide | Inferior PFS |
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 |
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 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 protocol 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 protocol PubMed
- Vermorken JB, Zanetta G, De Oliveira CF, 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 verified protocol 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 verified protocol 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 protocol PubMed NCT00770874
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine, Cisplatin
Regimen
Study | Years 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 |
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 verified protocol link to PMC article PubMed NCT00064077
Cisplatin & Ifosfamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Omura et al. 1997 (GOG 110) | 1990-1994 | Phase 3 (E-esc) | Cisplatin | Superior PFS |
Cisplatin & Mitolactol | Not reported | |||
Bloss et al. 2002 (GOG 149) | 1994-1997 | Phase 3 (C) | CIB | Did not meet primary endpoint of ORR |
Chemotherapy
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 protocol 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 | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Wagenaar et al. 2001 | NR in abstract | 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 medications
- 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 (Platinol)
- Furosemide (Lasix) (route/dose not specified) once on day 1, prior to chemotherapy
- Mannitol IV push once on day 1, prior to Cisplatin (Platinol)
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 verified protocol PubMed
Cisplatin & Paclitaxel
PC: Paclitaxel & Cisplatin
CP: Cisplatin & Paclitaxel
TP: Taxol (Paclitaxel) & Platinol (Cisplatin)
Regimen variant #1, 50/135, 3 hr paclitaxel
Study | Years 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moore et al. 2004 (GOG 169) | 1997-1999 | Phase 3 (E-esc) | Cisplatin | Superior PFS |
Monk et al. 2009 (GOG 204) | 2003-2007 | Phase 3 (C) | 1. Cisplatin & Gemcitabine | Seems to have superior PFS |
2. Cisplatin & Topotecan | Did not meet primary endpoint of OS | |||
3. Cisplatin & Vinorelbine | Might have superior PFS | |||
Kitagawa et al. 2015 (JCOG0505) | 2006-2009 | Phase 3 (C) | Carboplatin & Paclitaxel | Non-inferior OS Median OS: 18.3 vs 17.5 mo (HR 0.994, 90% CI 0.79-1.25) |
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 medications
- (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 | Years 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) | 1. CP & Pembrolizumab 2. CP, Bevacizumab, Pembrolizumab 3. Cisplatin, Paclitaxel, Pembrolizumab 4. 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 verified protocol 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 verified protocol 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 verified protocol link to PMC article PubMed 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. 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 verified protocol 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 verified protocol PubMed NCT03635567
Cisplatin, Paclitaxel, Bevacizumab
CP+Bev: Cisplatin, Paclitaxel, Bevacizumab
ESMO-preferred (I-A, 2017) |
Regimen variant #1, 135 mg/m2 paclitaxel
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (E-RT-esc) | 1. Cisplatin & Paclitaxel | Superior OS1 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (E-RT-esc) | 1. Cisplatin & Paclitaxel | Superior OS1 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) | 1. CP & Pembrolizumab 2. CP, Bevacizumab, Pembrolizumab 3. Cisplatin, Paclitaxel, Pembrolizumab 4. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
1Reported efficacy marked 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. 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 verified protocol link to PMC article PubMed 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. 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 verified protocol PubMed NCT03635567
- BEATcc: NCT03556839
Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1. CP 2. CP & Bevacizumab 3. Cisplatin & Paclitaxel 4. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 OS24: 50.4% vs 40.4% (HR 0.67, 95% CI 0.54-0.84) |
1Reported efficacy is for the ITT population
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 verified protocol PubMed NCT03635567
Cisplatin, Paclitaxel, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1. CP 2. CP & Bevacizumab 3. Cisplatin & Paclitaxel 4. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 OS24: 50.4% vs 40.4% (HR 0.67, 95% CI 0.54-0.84) |
1Reported efficacy is for the ITT population
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 verified protocol PubMed NCT03635567
Cisplatin & Topotecan
TC: Topotecan & Cisplatin
CT: Cisplatin & Topotecan
Regimen
Study | Years 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 |
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 verified protocol 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 verified protocol 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 verified protocol PubMed NCT00532818
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
VC: Vinorelbine, Cisplatin
Regimen
Study | Years 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 | |||
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 verified protocol link to PMC article PubMed NCT00064077
Ifosfamide monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Coleman et al. 1986 | NR in abstract | Phase 2 |
Sutton et al. 1993a | NR in abstract | Phase 2 |
Sutton et al. 1993b | NR in abstract | Phase 2 |
Chemotherapy
- 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 1200 mg/m2
- Dose could be increased by 300 mg/m2 or decreased by 20% depending on toxicity
Supportive medications
- 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
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 verified protocol PubMed
Paclitaxel monotherapy
Regimen variant #1, 135 mg/m2
Study | Years 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
- Dose could be changed to 110 or 200 mg/m2 depending on toxicity
Supportive medications
- Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
21-day cycles
Regimen variant #2, 170 mg/m2
Study | Years of enrollment | Evidence |
---|---|---|
McGuire et al. 1996 | 1990 | Phase 2 |
Curtin et al. 2001 | 1994 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 170 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Dosage for patients with previous pelvic radiation was 135 mg/m2
- Dose could be changed to 110 or 200 mg/m2 depending on toxicity
Supportive medications
- Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
21-day cycles
Regimen variant #3, 250 mg/m2
Study | Years of enrollment | Evidence |
---|---|---|
Kudelka et al. 1996 | NR | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 250 mg/m2 IV over 3 hours once on day 1
- Dose could be changed to 275, 225, or 200 mg/m2 depending on toxicity
Supportive medications
- Dexamethasone (Decadron) 20 mg PO for two doses on day 1; 14 and 7 hours prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 2, 24 hours after Paclitaxel (Taxol), given until day 19 or until ANC greater or equal to 10,000/uL
21-day cycles
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 verified protocol 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 verified protocol PubMed content property of 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. 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 verified protocol PubMed
Paclitaxel & Topotecan
TP: Topotecan, Paclitaxel
Regimen
Study | Years 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 verified protocol link to PMC article PubMed 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. link to original article PubMed
Paclitaxel, Topotecan, Bevacizumab
TP+Bev: Topotecan, Paclitaxel, Bevacizumab
Regimen
Study | Years 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 verified protocol link to PMC article PubMed 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. link to original article PubMed
Topotecan monotherapy
Regimen variant #1, q3wk
Study | Years of enrollment | Evidence |
---|---|---|
Bookman et al. 2000 (GOG 127-F) | NR in abstract | 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 | Years of enrollment | Evidence |
---|---|---|
Muderspach et al. 2001 (GOG 76-U) | NR in abstract | 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 verified protocol 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 verified protocol PubMed
Vinorelbine monotherapy
Regimen
Study | Years 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 verified protocol PubMed
Advanced or metastatic disease, subsequent lines of therapy
Bevacizumab monotherapy
Regimen
Study | Years 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 verified protocol link to PMC article PubMed
Cemiplimab monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 (C) | Phase 3 (E-switch-ooc) | 1. Pemetrexed 2. Topotecan 3. Irinotecan 4. Gemcitabine 5. Vinorelbine |
Superior OS 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 verified protocol PubMed NCT03257267
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine, Cisplatin
Regimen
Study | Years 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 verified protocol PubMed
Docetaxel monotherapy
Regimen variant #1, 36 mg/m2, 3 weeks out of 4
Study | Years of enrollment | Evidence |
---|---|---|
Garcia et al. 2008 | NR in abstract | Phase 2 |
Chemotherapy
- Docetaxel (Taxotere) 36 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
Supportive medications
- 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 | Years of enrollment | Evidence |
---|---|---|
Garcia et al. 2007 | NR in abstract | 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 protocol 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 verified protocol PubMed
FULV
FULV: 5-FU & LeucoVorin (Folinic acid)
Regimen variant #1, 1850/200
Study | Years 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
- Folinic acid (Leucovorin) 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 | Years of enrollment | Evidence |
---|---|---|
Look et al. 1992 | NR in abstract | Phase 2 |
Chemotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV once per day on days 1 to 5, given second
- Folinic acid (Leucovorin) 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 verified protocol 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 verified protocol PubMed
Gemcitabine monotherapy
Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Schilder et al. 2000 (GOG 127-K) | NR in abstract | Phase 2 |
Schilder et al. 2005 | NR in abstract | 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 (C) | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 verified protocol 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 verified protocol 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 verified protocol PubMed NCT03257267
- innovaTV 301: NCT04697628
Irinotecan monotherapy
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 (C) | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verschraegen et al. 1997 | 1993-1995 | Phase 2 | ||
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 medications
- Diphenhydramine (Benadryl) 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion
- Atropine 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 verified protocol 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 verified protocol PubMed NCT03257267
- innovaTV 301: NCT04697628
Pembrolizumab monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Chung et al. 2019 (KEYNOTE-158) | 2016 | Phase 2 (RT) |
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: 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 protocol PubMed NCT02628067
Pemetrexed monotherapy
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 (C) | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 | Years 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 medications
- Folic acid (Folate) 350 to 600 mcg PO once per day, starting 7 days before Pemetrexed (Alimta), to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days before Pemetrexed (Alimta), 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 (Alimta)
- 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 verified protocol 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 verified protocol PubMed NCT03257267
- innovaTV 301: NCT04697628
Tisotumab vedotin monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Coleman et al. 2021 (innovaTV 204) | 2018-2019 | Phase 2 (RT) |
Chemotherapy
- 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 protocol PubMed NCT03438396
Topotecan monotherapy
Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 (C) | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 verified protocol PubMed NCT03257267
- innovaTV 301: NCT04697628
Vinorelbine monotherapy
Regimen
Study | Years 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 (C) | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-ongoing | Phase 3 (C) | Tisotumab vedotin | Ongoing |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT 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 verified protocol 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 verified protocol 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 verified protocol PubMed NCT03257267
- innovaTV 301: NCT04697628