Ovarian cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main ovarian cancer page for current regimens.

21 regimens on this page
28 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

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 contains dosing details in abstract PubMed

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 superior DFS

Chemotherapy

References

  1. 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 PubMed

First-line chemotherapy for advanced stage disease

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

Altretamine & Cisplatin

Regimen

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

References

  1. 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 PubMed

CAP (Platinol)

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 Superior CR rate
Alberts et al. 1989 (SWOG S7925) 1979-1984 Phase 3 (C) 1. DC & BCG Superior OS
2. DCP & BCG Did not meet endpoint of OS
Bolis et al. 1987 1980-1985 Phase 3 (E-esc) 1. Cisplatin
2. CP 		Seems to have superior 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 superior 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. Carboplatin
2. Carboplatin & Paclitaxel 		Did not meet primary endpoint of OS

Chemotherapy

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed
  5. 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 PubMed
  6. 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 PubMed
  7. 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 PubMed
  8. 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 contains dosing details in manuscript PubMed
  9. ICON3: Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. link to original article PubMed

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 superior OS
Swenerton et al. 1992 1985-1989 Phase 3 (E-RT-switch-ic) Cisplatin & Cyclophosphamide Did not meet primary endpoint of PFS

Chemotherapy

References

  1. 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 contains dosing details in abstract PubMed
  2. 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 contains dosing details in manuscript PubMed

CEP

CEP: Cyclophosphamide, Epirubicin, Platinol (Cisplatin)

Regimen

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
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

References

  1. 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 PubMed
  2. 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 PubMed

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 superior TTTF

Chemotherapy

References

  1. 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 PubMed

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

References

  1. 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 PubMed

Cisplatin monotherapy

Regimen

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

21-day cycle for 6 cycles

References

  1. 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 PubMed
  2. 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 contains dosing details in abstract PubMed
  3. 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 contains dosing details in abstract PubMed

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 inferior surgical CR rate

Chemotherapy

28-day cycle for 6 cycles


Regimen variant #2, 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 Inferior OS

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #3, 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

21-day cycle for 8 cycles


Regimen variant #4, 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

28-day cycle for 6 cycles


Regimen variant #5, 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 Inferior OS
Breitbach et al. 2002 1988-NR Phase 3 (C) Cisplatin & Treosulfan Did not meet primary endpoint of TTP
McGuire et al. 1996 (GOG 111) NR Phase 3 (C) Cisplatin & Paclitaxel Inferior OS
Piccart et al. 2000 (OV10) 1994-1995 Phase 3 (C) Cisplatin & Paclitaxel Inferior OS

Note: the dosing for Breitbach et al. 2002 could not be confirmed from the abstract.

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #6, 100/600

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Alberts et al. 1992 (SWOG 8412) 1985-1989 Phase 3 (C) Carboplatin & Cyclophosphamide Seems to have inferior OS
Dittrich et al. 2003 1990-1993 Phase 3 (C) Carboplatin & Cisplatin Did not meet co-primary endpoints of PFS/OS
Windbichler et al. 2000 1991-1997 Phase 3 (C) Cisplatin, Cyclophosphamide, IFN gamma Seems to have inferior PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #7, 100/750

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kaye et al. 1992 1988-1991 Phase 3 (E-esc) Cisplatin & Cyclophosphamide; 50/750 Superior OS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #8, 100/1000

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Misset et al. 2001 NR Phase 2/3 (C) Cyclophosphamide & Oxaliplatin Did not meet endpoints of PFS/OS

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 contains dosing details in abstract PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 contains dosing details in abstract PubMed
  5. 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 contains dosing details in manuscript PubMed
  6. 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 contains dosing details in abstract PubMed
  7. 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 PubMed
  8. 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 contains dosing details in manuscript PubMed
  9. 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 contains dosing details in abstract PubMed
  10. 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 contains dosing details in manuscript PubMed
  11. 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 contains dosing details in abstract PubMed
  12. 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. PubMed
  13. 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 contains dosing details in abstract PubMed
  14. 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 PubMed

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 superior PFS

Chemotherapy

Immunotherapy

References

  1. 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 PubMed

Hexa-CAF

Hexa-CAF: Hexalen (Altretamine), Cyclophosphamide, Adrucil (Fluorouracil), Folex (Methotrexate)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Young et al. 1978 1972-1977 Phase 3 (E-esc) Melphalan Superior OS
Neijt et al. 1984 1979-1981 Phase 3 (C) CHAP-5 Inferior OS

Chemotherapy

References

  1. 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 PubMed
  2. 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 PubMed

Melphalan monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Park et al. 1980 (GOG 3) 1971-1976 Phase 3 (C) 1. 5-FU & Melphalan
2. 5-FU, Dactinomycin, Melphalan
3. 5-FU, Cyclophosphamide, Dactinomycin 		Did not meet endpoints of PFS/OS
Young et al. 1978 1972-1977 Phase 3 (C) Hexa-CAF Inferior 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 & Melphalan
2. AC 		Seems to have inferior CR rate
Wadler et al. 1996 (ECOG E2878) 1978-1980 Phase 3 (C) CHAD Seems to have inferior TTTF

Chemotherapy

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed
  5. 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 PubMed

Maintenance after first-line therapy

Altretamine monotherapy

Regimen

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

Chemotherapy

28-day cycle for 6 cycles

References

  1. 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 contains dosing details in abstract PubMed
    1. Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article PubMed

Second-line therapy

Altretamine & Cisplatin

Regimen

Study Evidence
Vogl et al. 1979 Non-randomized

Chemotherapy

References

  1. 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 PubMed

CAP (Platinol)

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 superior OS

Chemotherapy

References

  1. Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. link to original article PubMed

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

Continued indefinitely

References

  1. 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 PubMed NCT00041080

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 PFS

Chemotherapy

7-day cycles

References

  1. 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 contains dosing details in manuscript PubMed NCT00382811

Niraparib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Moore et al. 2019 (QUADRA) 2015-2017 Phase 2 (RT)

Targeted therapy

28-day cycles

References

  1. 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 contains dosing details in abstract PubMed NCT02354586

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence
Gelmon et al. 2011 (D0810C00020) 2008-2009 Phase 2

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed

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 Superior PFS (primary endpoint)
Median PFS: 7.4 vs 5.7 mo
(HR 0.64, 95% CI 0.49-0.84)

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

Continued indefinitely

References

  1. 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 PubMed NCT01482715
    1. 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 PubMed
  2. 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 contains dosing details in abstract PubMed NCT02855944

Intraperitoneal therapy

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 superior OS

Chemotherapy

References

  1. 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 PubMed
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