Ovarian cancer - historical

Back to Top
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main ovarian cancer page for current regimens.
Last updated on 2024-07-23:26 regimens on this page
45 variants on this page
 
=Adjuvant chemotherapy for early stage disease=
==Cisplatin & Cyclophosphamide==
CP: Cyclophosphamide & Platinol (Cisplatin)
PC: Platinol (Cisplatin) & Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Young et al. 2003 (GOG 95)	1986-1994 	Phase 3 (C)	IP P32 	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===References===
# GOG 95: Young RC, Brady MF, Nieberg RK, Long HJ, Mayer AR, Lentz SS, Hurteau J, Alberts DS. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a Gynecologic Oncology Group study. J Clin Oncol. 2003 Dec 1;21(23):4350-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Melphalan monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Klaassen et al. 1988	1975-1984 	Phase 3 (E-switch-ooc)	WAI 	Seems to have longer DFS
====Chemotherapy====
*Melphalan (Alkeran) 8 mg/m2 PO once per day on days 1 to 4
28-day cycle for 18 cycles
===References===
# Klaassen D, Shelley W, Starreveld A, Kirk M, Boyes D, Gerulath A, Levitt M, Fraser R, Carmichael J, Methot Y, Willan A; National Cancer Institute of Canada Clinical Trials Group. Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report. J Clin Oncol. 1988 Aug;6(8):1254-63. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
=First-line chemotherapy for advanced stage disease=
Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.
==Altretamine & Cisplatin (HD)==
HD: Hexamethylmelamine (Altretamine) & DDP (Cisplatin)
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wiernik et al. 1992a	1979-1985 	Randomized (E-RT-de-esc)	Altretamine, Cisplatin, Pyridoxine	Not clearly reported
====Chemotherapy====
*Altretamine (Hexalen) 200 mg/m2 PO once per day on days 8 to 21
*Cisplatin (Platinol) 37.5 mg/m2 IV once on day 1
21-day cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wiernik et al. 1992a	1979-1985 	Randomized (E-RT-de-esc)	Altretamine, Cisplatin, Pyridoxine	Not clearly reported
====Chemotherapy====
*Altretamine (Hexalen) 200 mg/m2 PO once per day on days 8 to 21
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycles
===References===
# Wiernik PH, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J; ECOG. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992;10(1):1-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Carboplatin & Cyclophosphamide==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Alberts et al. 1992 (SWOG 8412)	1985-1989 	Phase 3 (E-RT-switch-ic)	Cisplatin & Cyclophosphamide	Seems to have longer OS
Swenerton et al. 1992 	1985-1989 	Phase 3 (E-RT-switch-ic)	Cisplatin & Cyclophosphamide	Did not meet primary endpoint of PFS
====Chemotherapy====
*Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===References===
# SWOG 8412: Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CEP==
CEP: Cyclophosphamide, Epirubicin, Platinol (Cisplatin)
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wils et al. 1999	1988-1995 	Phase 3 (C)	EP 	Did not meet endpoints of pCR rate/OS
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
*Epirubicin (Ellence) 75 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ray-Coquard et al. 2007	1994-1997 	Phase 3 (C)	CEP; intensified	Did not meet primary endpoint of OS24
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
*Epirubicin (Ellence) 50 mg/m2 IV once on day 1
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===References===
# Wils J, van Geuns H, Stoot J, Bergmans M, Boschma F, Bron H, Degen J, Erdkamp F, van Erp J, Haest J, Iding R, Lalisang F, de Pree N, de Rooy C, Snijders M, Schepers J, Vreeswijk J, Wals J, Werter M, Wetzels L, Smeets J, Schouten L. Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg. Anticancer Drugs. 1999 Mar;10(3):257-61. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Ray-Coquard I, Paraiso D, Guastalla JP, Leduc B, Guichard F, Martin C, Chauvenet L, Haddad-Guichard Z, Lepillé D, Orfeuvre H, Gautier H, Castera D, Pujade-Lauraine E; GINECO. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group. Br J Cancer. 2007 Nov 5;97(9):1200-5. Epub 2007 Oct 9. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC
==CHAD==
CHAD: Cyclophosphamide, Hexalen (Altretamine), Adriamycin (Doxorubicin), DDP (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wadler et al. 1996 (ECOG E2878)	1978-1980 	Phase 3 (E-esc)	Melphalan 	Seems to have longer TTTF
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Altretamine (Hexalen) 150 mg/m2 PO once per day on days 8 to 21
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
28-day cycles
===References===
# ECOG E2878: Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Chlorambucil & Cisplatin==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Barker & Wiltshaw 1981	1976-1979 	Phase 3 (C)	Chlorambucil, Cisplatin, Doxorubicin	Did not meet endpoint of ORR
====Chemotherapy====
*Chlorambucil (Leukeran) 0.15 mg/kg PO once per day on days 2 to 8
*Cisplatin (Platinol) 20 mg/m2 IV once on day 1
21-day cycle for 12 cycles
===References===
# Barker GH, Wiltshaw E. Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Lancet. 1981 Apr 4;1(8223):747-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CISCA==
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
DCP: Doxorubicin, Cyclophosphamide, Platinol (Cisplatin)
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Omura et al. 1986 (GOG 47) 	1979-1982 	Phase 3 (E-esc)	AC 	Higher CR rate 	
Alberts et al. 1989 (SWOG S7925)	1979-1984 	Phase 3 (C) 	1. DC & BCG 	Longer OS 	
Alberts et al. 1989 (SWOG S7925)	1979-1984 	Phase 3 (C) 	2. DCP & BCG 	Did not meet endpoint of OS 	
Bolis et al. 1987 	1980-1985 	Phase 3 (C) 	1. Cisplatin2. CP 	Seems to have longer PFS 	
Omura et al. 1989 (GOG 52) 	1981-1985 	Phase 3 (E-esc)	CP 	Did not meet primary endpoint of PFS24	
Conte et al. 1986 	1982-1984 	Phase 3 (E-esc)	CP 	Seems to have higher surgical CR rate 	
Creasman et al. 1990 (GOG 60) 	1982-1986 	Phase 3 (C) 	CAP & BCG 	Did not meet endpoints of PFS/OS 	
Parmar et al. 1998 (ICON2) 	1991-1996 	Phase 3 (C) 	Carboplatin 	Did not meet primary endpoint of OS 	More toxic
Parmar et al. 2002 (ICON3) 	1995-1998 	Phase 3 (C) 	1. Carboplatin2. Carboplatin & Paclitaxel	Did not meet primary endpoint of OS 	
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 6 cycles
===References===
# GOG 47: Omura G, Blessing JA, Ehrlich CE, Miller A, Yordan E, Creasman WT, Homesley HD. A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma: a Gynecologic Oncology Group study. Cancer. 1986 May 1;57(9):1725-30. link to original article EuroPMC
# Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. link to original article EuroPMC
# Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SWOG S7925: Alberts DS, Mason-Liddil N, O'Toole RV, Abbott TM, Kronmal R, Hilgers RD, Surwit EA, Eyre HJ, Baker LH. Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: a Southwest Oncology Group Study. Gynecol Oncol. 1989 Jan;32(1):8-15. link to original article EuroPMC
# GOG 52: Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. link to original article EuroPMC
# GOG 60: Creasman WT, Omura GA, Brady MF, Yordan E, DiSaia PJ, Beecham J. A randomized trial of cyclophosphamide, doxorubicin, and cisplatin with or without bacillus Calmette-Guerin in patients with suboptimal stage III and IV ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):239-43. link to original article EuroPMC
# Meta-analysis: The Ovarian Cancer Meta-Analysis Project. Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol. 1991 Sep;9(9):1668-74. link to original article EuroPMC
# ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# ICON3: Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. link to original article EuroPMC
==Cisplatin monotherapy==
===Regimen variant #1, 50 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Bolis et al. 1987	1980-1985 	Phase 3 (E-de-esc)	1. CAP2. CP	Did not meet endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 6 cycles
===Regimen variant #2, 75 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fruscio et al. 2011	1988-1992 	Phase 3 (C)	Cisplatin; weekly	Did not meet primary endpoint of PFS
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #3, 100 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mangioni et al. 1989	1985-01 to 1987-02 	Phase 3 (C)	Carboplatin	Did not meet endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV over 30 minutes once on day 1
1-month cycle for 5 cycles
===Regimen variant #4, 100 mg/m2 with step-down===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Taylor et al. 1994	1981-10 to 1984-06 	Phase 3 (C)	Carboplatin	Did not meet endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 5: 100 mg/m2 IV once on day 1
**Cycles 6 to 10: 30 mg/m2 IV once on day 1
28-day cycle for 10 cycles
===References===
# Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Fruscio R, Garbi A, Parma G, Lissoni AA, Garavaglia D, Bonazzi CM, Dell'anna T, Mangioni C, Milani R, Colombo N. Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer. J Natl Cancer Inst. 2011 Feb 16;103(4):347-51. Epub 2011 Jan 7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Cisplatin & Cyclophosphamide==
CP: Cyclophosphamide & Platinol (Cisplatin)
CPC: CisPlatin & Cyclophosphamide
PC: Platinol (Cisplatin) & Cyclophosphamide
===Regimen variant #1, 50/600===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Conte et al. 1986	1982-1984 	Phase 3 (C)	PAC 	Seems to have lower surgical CR rate
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===Regimen variant #2, 50/650===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Bolis et al. 1987	1980-1985 	Phase 3 (E-de-esc)	1. Cisplatin2. CAP	Did not meet endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===Regimen variant #3, 50/750===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kaye et al. 1992	1988-1991 	Phase 3 (E-de-esc)	Cisplatin & Cyclophosphamide; 100/750	Shorter OS
====Preceding treatment====
*GOG 111: Primary debulking surgery, with suboptimal debulking
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #4, 50/1000===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Omura et al. 1989 (GOG 52)	1981-1985 	Phase 3 (C)	CAP 	Did not meet primary endpoint of PFS24
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 8 cycles
===Regimen variant #5, 75/600===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Swenerton et al. 1992	1985-1989 	Phase 3 (C)	Carboplatin & Cyclophosphamide	Did not meet primary endpoint of PFS
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===Regimen variant #6, 75/700===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mouratidou et al. 2007	1998-2002 	Phase 3 (C)	Cisplatin & Paclitaxel	Did not meet primary endpoint of PFS
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #7, 75/750===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
van der Burg et al. 1995 	1987-1993 	Phase 3 (C)	Cisplatin & Cyclophosphamide, with interval debulking	Shorter OS
Breitbach et al. 2002 	1988 to not reported	Phase 3 (C)	Cisplatin & Treosulfan 	Did not meet primary endpoint of TTP
McGuire et al. 1996 (GOG 111)	Not reported 	Phase 3 (C)	Cisplatin & Paclitaxel 	Shorter OS
Piccart et al. 2000 (OV10) 	1994-04 to 1995-08 	Phase 3 (C)	Cisplatin & Paclitaxel 	Shorter OS
Note: the dosing for Breitbach et al. 2002 could not be confirmed from the abstract.
====Preceding treatment====
*GOG 111: Primary debulking surgery, with suboptimal debulking
*OV10: Primary debulking surgery, with optimal or suboptimal debulking
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #8, 100/600 q3wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Alberts et al. 1992 (SWOG 8412)	1985-1989 	Phase 3 (C)	Carboplatin & Cyclophosphamide 	Seems to have shorter OS
Alberts et al. 1996 (GOG 104) 	1986-1992 	Phase 3 (C)	Cisplatin (IP) & Cyclophosphamide	Seems to have shorter OS
Dittrich et al. 2003 	1990-1993 	Phase 3 (C)	Carboplatin & Cisplatin 	Did not meet co-primary endpoints of PFS/OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on either day 1 or 2
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 60 to 90 minutes once on day 1
21-day cycle for 6 cycles
===Regimen variant #9, 100/600 q4wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Windbichler et al. 2000	1991-1997 	Phase 3 (C)	Cisplatin, Cyclophosphamide, IFN gamma	Seems to have shorter PFS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
===Regimen variant #10, 100/750===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kaye et al. 1992	1988-1991 	Phase 3 (E-esc)	Cisplatin & Cyclophosphamide; 50/750	Longer OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #11, 100/1000===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Misset et al. 2001	Not reported 	Phase 2/3 (C)	Cyclophosphamide & Oxaliplatin	Did not meet endpoints of PFS/OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===References===
# Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 52: Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. link to original article EuroPMC
# SWOG 8412: Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Kaye SB, Lewis CR, Paul J, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Atkinson RJ, Soukop M, Rankin EM, Cassidy J, Davis JA, Reed NS, Crawford SM, MacLean A, Swapp GA, Sarkar TK, Kennedy JH, Symonds RP. Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. Lancet. 1992 Aug 8;340(8815):329-33. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S; Gynecological Cancer Cooperative Group of the European Organisation for Research and Treatment of Cancer. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med. 1995 Mar 9;332(10):629-34. link to original article EuroPMC
# GOG 111: McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 104: Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# OV10: Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Misset JL, Vennin P, Chollet PH, Pouillart P, Laplaige PH, Frobert JL, Castera D, Fabbro M, Langlois D, Cortesi E, Lucas V, Gamelin E, Laadem A, Otero J. Multicenter phase II-III study of oxaliplatin plus cyclophosphamide vs cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients. Ann Oncol. 2001 Oct;12(10):1411-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Breitbach GP, Meden H, Schmid H, Kühn W, Sass G, Schach S, Schmidt-Rohde P, Bastert G; GTOC Study Group. Treosulfan in the treatment of advanced ovarian cancer: a randomised co-operative multicentre phase III-study. Anticancer Res. 2002 Sep-Oct;22(5):2923-32. EuroPMC
# Dittrich Ch, Sevelda P, Salzer H, Obermair A, Speiser P, Breitenecker G, Schemper M, Kaider A; Austrian Ovarian Cancer Study Group. Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients: 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin. Eur J Cancer. 2003 May;39(8):1129-40. Erratum in: Eur J Cancer. 2004 Mar;40(4):627. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Cisplatin, Cyclophosphamide, Interferon gamma-1b==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Windbichler et al. 2000	1991-1997 	Phase 3 (E-esc)	Cisplatin & Cyclophosphamide	Seems to have longer PFS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 2
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 2
====Immunotherapy====
*Interferon gamma-1b (Actimmune) 0.1 mg SC once per day on days 1, 3, 5, 15, 17, 19
28-day cycle for 6 cycles
===References===
# Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Hexa-CAF==
Hexa-CAF: Hexalen (Altretamine), Cyclophosphamide, Adrucil (Fluorouracil), Folex (Methotrexate)
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Neijt et al. 1984	1979-1981 	Phase 3 (C)	CHAP-5 	Shorter OS
====Chemotherapy====
*Altretamine (Hexalen) 150 mg/m2 PO once per day on days 1 to 14
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
28-day cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Young et al. 1978	1972-1977 	Phase 3 (E-esc)	Melphalan 	Longer OS
====Chemotherapy====
*Altretamine (Hexalen) 150 mg/m2 PO once per day on days 1 to 14
*Cyclophosphamide (Cytoxan) 150 mg/m2 PO once per day on days 1 to 14
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
Monthly cycle for 6 or more cycles
===References===
# Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Vriesendorp R, Kooyman CD, van Lindert AC, Hamerlynck JV, van Lent M, van Houwelingen JC, Pinedo HM. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984 Sep 15;2(8403):594-600. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Melphalan monotherapy==
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Young et al. 1978	1972-1977 	Phase 3 (C)	Hexa-CAF 	Shorter OS
====Chemotherapy====
*Melphalan (Alkeran) 0.2 mg/kg PO once per day on days 1 to 5
28- to 35-day cycles, interval based on count recovery
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Park et al. 1980 (GOG 3) 	1971-1976 	Phase 3 (C)	1. 5-FU & Melphalan2. 5-FU, Dactinomycin, Melphalan3. 5-FU, Cyclophosphamide, Dactinomycin	Did not meet endpoints of PFS/OS
Miller et al. 1980 	1974-1977 	Phase 3 (C)	5-FU, Melphalan, MTX 	Did not meet endpoints of ORR/OS
Omura et al. 1983 (GOG 22) 	1976-1979 	Phase 3 (C)	1. Altretamine & Melphalan2. AC 	Seems to have lower CR rate
Wadler et al. 1996 (ECOG E2878)	1978-1980 	Phase 3 (C)	CHAD 	Seems to have shorter TTTF
====Chemotherapy====
*Melphalan (Alkeran) 3.5 mg/m2 PO twice per day on days 1 to 5
28-day cycles
===References===
# Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 3: Park RC, Blom J, Disaia PJ, Lagasse LD, Blessing JA. Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone in combination with 5-fluorouracil and dactinomycin or with the combination of cytoxan, 5-fluorouracil and dactinomycin. Cancer. 1980 May 15;45(10):2529-42. link to original article EuroPMC
# Miller AB, Klaassen DJ, Boyes DA, Dodds DJ, Gerulath A, Kirk ME, Levitt M, Pearson JG, Wall C. Combination v sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer. Can Med Assoc J. 1980 Sep 6;123(5):365-71. link to original article EuroPMC
# GOG 22: Omura GA, Morrow CP, Blessing JA, Miller A, Buchsbaum HJ, Homesley HD, Leone L. A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma. Cancer. 1983 Mar 1;51(5):783-9. link to original article EuroPMC
# ECOG E2878: Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Maintenance after first-line therapy=
==Altretamine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Rothenberg et al. 2001 (SWOG-9326)	1993-1997 	Phase 2
====Chemotherapy====
*Altretamine (Hexalen) 260 mg/m2/day PO on days 1 to 14, split into 4 daily doses
28-day cycle for 6 cycles
===References===
# SWOG-9326: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article EuroPMC
=Second-line therapy for relapsed or recurrent disease, platinum-sensitive=
==Rucaparib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Swisher et al. 2016 (ARIEL2)	2013-10-30 to 2014-12-19	Phase 2 (RT)
Note: the MCBS score is for the BRCA-mutated subgroup, only.
====Targeted therapy====
*Rucaparib (Rubraca) 600 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# ARIEL2: Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01891344
##Pooled subgroup analysis: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. link to original article EuroPMC
=Second-line therapy=
==Altretamine & Cisplatin (HD)==
HD: Hexamethylmelamine (Altretamine) & DDP (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Vogl et al. 1979	1976-1977 	Non-randomized
====Chemotherapy====
*Altretamine (Hexalen) 200 mg/m2/day PO on days 8 to 21, in divided doses
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
21-day cycles
===References===
# Vogl SE, Greenwald E, Kaplan BH, Moukhtar M, Wollner D. Ovarian cancer: effective treatment after alkylating-agent failure. JAMA. 1979 May 4;241(18):1908-11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CISCA==
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cantù et al. 1999	1992-1995 	Phase 3 (C)	Paclitaxel	Seems to have longer OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
21-day cycle for at least 6 cycles
===References===
# Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Tamoxifen monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hurteau et al. 2010 (GOG 198)	2003-2007 	Phase 3 (C)	Thalidomide	Did not meet primary endpoint of PFS
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Endocrine therapy====
*Tamoxifen (Nolvadex) 20 mg PO twice per day on days 1 to 28
28-day cycle for up to 12 cycles
===References===
# GOG 198: Hurteau JA, Brady MF, Darcy KM, McGuire WP, Edmonds P, Pearl ML, Ivanov I, Tewari KS, Mannel RS, Zanotti K, Benbrook DM. Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): A Gynecologic Oncology Group study. Gynecol Oncol. 2010 Dec;119(3):444-50. Epub 2010 Sep 17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00041080
=Maintenance after second-line therapy for platinum-sensitive disease=
==Niraparib monotherapy==
===Regimen variant #1, 200 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2021 (NORA)	2017-2019 	Phase 3 (E-esc)	Placebo 	Longer PFS (primary endpoint)Median PFS: 18.3 vs 5.4 mo(HR 0.32, 95% CI 0.23-0.45)
Note: after a mid-protocol amendment, this was the dosing for patients with bodyweight of less than 77 kg, or a platelet count of less than 150 x 109/L.
====Preceding treatment====
*Second-line platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
====Targeted therapy====
*Niraparib (Zejula) 200 mg PO once per day on days 1 to 28
28-day cycles
===Regimen variant #2, 300 mg/day===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Mirza et al. 2016 (NOVA)	2013 to not reported	Phase 3 (E-RT-esc)	Placebo 	Longer PFS (primary endpoint)1Median PFS: 9.3 vs 3.9 mo(HR 0.45, 95% CI 0.34-0.61)
Wu et al. 2021 (NORA) 	2017-2019 	Phase 3 (E-esc) 	Placebo 	Longer PFS (primary endpoint)Median PFS: 18.3 vs 5.4 mo(HR 0.32, 95% CI 0.23-0.45)
1Reported efficacy is for the overall non-gBRCAm cohort.
Note: in NORA, after a mid-protocol amendment, this was the dosing for patients with bodyweight of 77 kg or more, and a platelet count of 150 x 109/L or more.
====Preceding treatment====
*Second-line platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
====Targeted therapy====
*Niraparib (Zejula) 300 mg PO once per day on days 1 to 28
28-day cycles
===References===
# NOVA: Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01847274
## PRO analysis: Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vázquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. Epub 2018 Jul 17. link to original article EuroPMC
## Subgroup analysis: Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. Epub 2019 Jun 7. link to original article link to PMC article EuroPMC
## Update: Mirza MR, Benigno B, Dørum A, Mahner S, Bessette P, Barceló IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Casado Herráez A, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. Epub 2020 Sep 25. link to original article EuroPMC
# NORA: Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, Wu LY, Liu ZL, Gao YN, Wang DB, Lou G, Yang HY, Zhou Q, Kong BH, Huang Y, Chen LP, Li GL, An RF, Wang K, Zhang Y, Yan XJ, Lu X, Lu WG, Hao M, Wang L, Cui H, Chen QH, Abulizi G, Huang XH, Tian XF, Wen H, Zhang C, Hou JM, Mirza MR. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021 Apr;32(4):512-521. Epub 2021 Jan 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03705156
##Update: Wu X, Zhu J, Yin R, Yang J, Liu J, Wang J, Wu L, Liu Z, Gao Y, Wang D, Lou G, Yang H, Zhou Q, Kong B, Huang Y, Chen L, Li G, An R, Wang K, Zhang Y, Yan X, Lu X, Lu W, Hao M, Wang L, Cui H, Chen Q, Abulizi G, Huang X, Tian X, Wen H, Huang Z, Dong J, Zhang C, Hou J, Mirza MR. Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial. EClinicalMedicine. 2024 May 7;72:102629. link to original article link to PMC article EuroPMC
==Olaparib monotherapy==
===Regimen variant #1, 600 mg/day===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Pujade-Lauraine et al. 2023 (OReO)	2017-06-28 to 2021-02-10	Phase 3b (E-esc)	Placebo 	Longer PFS1 (primary endpoint)Median PFS: 5.3 vs 2.8 mo(HR 0.43, 95% CI 0.26-0.71)
1Reported efficacy is for the non-BRCA-mutated cohort.
====Preceding treatment====
*Second-line platinum-based chemotherapy
====Targeted therapy====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===Regimen variant #2, 800 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ledermann et al. 2012 (Study 19)	2008-2010 	Randomized Phase 2 (E-RT-esc)	Placebo 	Might have longer OS (secondary endpoint)1Median OS: 29.8 vs 27.8 mo(HR 0.73, 95% CI 0.55-0.95)Longer PFS (primary endpoint)Median PFS: 8.4 vs 4.8 mo(HR 0.35, 95% CI 0.25-0.49)
1Reported efficacy for Study 19 is based on the 2018 update; although p=0.02, the authors state that "the predefined threshold for statistical significance was not met."
====Targeted therapy====
*Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
===References===
# Study 19: Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. Epub 2012 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00753545
## Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article EuroPMC
## HRQoL analysis: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. Epub 2016 Nov 8. link to original article link to PMC article EuroPMC
## Update: Friedlander M, Matulonis U, Gourley C, du Bois A, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Shirinkin V, Selle F, Fielding A, Lowe ES, McMurtry EL, Spencer S, Rowe P, Mann H, Parry D, Ledermann J. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 2018 Oct;119(9):1075-1085. Epub 2018 Oct 24. link to original article link to PMC article EuroPMC
#OReO: Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marmé F, Lindemann K, Colombo N, Mądry R, Glasspool R, Vergote I, Korach J, Lheureux S, Dubot C, Oaknin A, Zamagni C, Heitz F, Gladieff L, Rubio-Pérez MJ, Scollo P, Blakeley C, Shaw B, Ray-Coquard I, Redondo A; OReO/ENGOT-ov38 investigators. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023 Dec;34(12):1152-1164. Epub 2023 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03106987
#ICON9: NCT03278717
==Rucaparib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Coleman et al. 2017 (ARIEL3)	2014-2016 	Phase 3 (E-RT-esc)	Placebo 	Longer PFS (primary endpoint)Median PFS: 16.6 vs 5.4 mo(HR 0.23, 95% CI 0.16-0.34)
====Preceding treatment====
*Second-line platinum-containing chemotherapy
====Targeted therapy====
*Rucaparib (Rubraca) 600 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# ARIEL3: Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01968213
## Update: Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. link to original article link to PMC article EuroPMC
## Update: Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cella D, Meunier J, Goble S, Cameron T, Maloney L, Mörk AC, Bedel J, Ledermann JA, Coleman RL. Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma. J Clin Oncol. 2020 Oct 20;38(30):3494-3505. Epub 2020 Aug 24. link to original article link to PMC article EuroPMC
##PRO analysis: Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. Epub 2023 May 30. link to original article EuroPMC
=Relapsed or recurrent disease, platinum-resistant=
==Carboplatin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fotopoulou et al. 2013 (OVATURE)	2006-2009 	Phase 3 (C)	Carboplatin & Phenoxodiol	Did not meet primary endpoint of PFSMedian PFS: 20.1 vs 15.4 wk
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 2 IV once on day 1
7-day cycles
===References===
# OVATURE: Fotopoulou C, Vergote I, Mainwaring P, Bidzinski M, Vermorken JB, Ghamande SA, Harnett P, Del Prete SA, Green JA, Spaczynski M, Blagden S, Gore M, Ledermann J, Kaye S, Gabra H. Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study. Ann Oncol. 2014 Jan;25(1):160-5. Epub 2013 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00382811
==Niraparib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Moore et al. 2019 (QUADRA)	2015-2017 	Phase 2 (RT)
====Targeted therapy====
*Niraparib (Zejula) 300 mg PO once per day on days 1 to 28
28-day cycles
===References===
# QUADRA: Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02354586
==Olaparib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Gelmon et al. 2011 (D0810C00020)	2008-2009 	Phase 2
====Targeted therapy====
*Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
===References===
# D0810C00020: Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. Epub 2011 Aug 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Rucaparib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kristeleit et al. 2017 (Study 10)	2011-2013 	Phase 2 (RT) 	 	
Kristeleit et al. 2022 (ARIEL4) 	2017-2020 	Phase 3 (E-switch-ooc)	Standard-of-care chemotherapy	Longer PFS (primary endpoint)Median PFS: 7.4 vs 5.7 mo(HR 0.64, 95% CI 0.49-0.84)Seems to have shorter OS1 (secondary endpoint)Median OS: 19.4 vs 25.4 mo(HR 1.30, 95% CI 1.00-1.70)
1Reported efficacy for ARIEL4 is based on the 2025 update.
Note: the OS results of ARIEL4 prompted the withdrawal of this indication for rucaparib.
====Biomarker eligibility criteria====
*Study 10: Germline BRCA1 or BRCA2 mutation
*ARIEL4: BRCA1 or BRCA2 mutation
====Targeted therapy====
*Rucaparib (Rubraca) 600 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# Study 10: Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4095-4106. Epub 2017 Mar 6. link to orginal article EuroPMC NCT01482715
## Pooled subgroup analysis: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. link to original article EuroPMC
# ARIEL4: Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Apr;23(4):465-478. Epub 2022 Mar 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02855944
##Update: Oza AM, Lisyanskaya A, Fedenko A, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Kristeleit R. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Feb;26(2):249-264. link to original article link to EuroPMC
=Intraperitoneal therapy=
==IP Cisplatin & Cyclophosphamide==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Alberts et al. 1996 (GOG 104)	1986-1992 	Phase 3 (E-switch-ic)	Cisplatin (IV) & Cyclophosphamide	Seems to have longer OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IP once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 60 to 90 minutes once on day 1
21-day cycle for 6 cycles
===References===
# GOG 104: Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Ovarian cancer regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Gynecologic cancers