Ovarian cancer - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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.

24 regimens on this page 39 variants on this page

First-line chemotherapy for advanced stage disease

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

CAP (Platinol)

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CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Conte et al. 1986	Phase III (E)	CP	Seems not superior
Bolis et al. 1987	Phase III (E)	1. Cisplatin 2. CP	Seems to have superior PFS
Omura et al. 1989	Phase III (E)	CP	Seems not superior
Parmar et al. 1998 (ICON2)	Phase III (C)	Carboplatin	Seems not superior	More toxic
Parmar et al. 2002 (ICON3)	Phase III (C)	1. Carboplatin 2. Carboplatin & Paclitaxel	Seems not superior

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Doxorubicin (Adriamycin)
• Cisplatin (Platinol)

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 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. 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. 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
5. ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, and Williams C; ICON Collaborators. 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 verified protocol PubMed
6. 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

CEP

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CEP: Cyclophosphamide, Epirubicin, Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Ray-Coquard et al. 2007	Phase III (C)	Intensified CEP	Seems not superior

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Epirubicin (Ellence)
• Cisplatin (Platinol)

References

1. 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. 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

Cisplatin monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Fruscio et al. 2011	Phase III (C)	Weekly cisplatin	Seems not superior

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV once on day 1

21-day cycle for 6 cycles

References

1. 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 protocol PubMed

Cisplatin & Cyclophosphamide

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CP: Cisplatin & Platinol (Cisplatin)
PC: Platinol (Cisplatin) & Cyclophosphamide

Variant #1, 50/600

Study	Evidence	Comparator	Efficacy
Conte et al. 1986	Phase III (C)	PAC	Seems not superior

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

Variant #2, 50/750

Study	Evidence	Comparator	Efficacy
Kaye et al. 1992	Phase III (E)	Cisplatin & Cyclophosphamide 100/750	Inferior OS
McGuire et al. 1996 (GOG 111)	Phase III (E)	Cisplatin & Cyclophosphamide 100/750	Inferior 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

Variant #3, 50/1000

Study	Evidence	Comparator	Efficacy
Omura et al. 1989	Phase III (C)	CAP	Seems not superior

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

Variant #4, 75/600

Study	Evidence	Comparator	Efficacy
Swenerton et al. 1992	Phase III (C)	Carboplatin & Cyclophosphamide	Seems not superior

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

Variant #5, 75/750

Study	Evidence	Comparator	Efficacy
van der Burg et al. 1995	Phase III (C)	Cisplatin & Cyclophosphamide, with interval debulking	Inferior OS
McGuire et al. 1996 (GOG 111)	Phase III (C)	Cisplatin & Paclitaxel	Inferior OS
Piccart et al. 2000 (OV10)	Phase III (C)	Cisplatin & Paclitaxel	Inferior OS

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

Variant #6, 100/600

Study	Evidence	Comparator	Efficacy
Alberts et al. 1992	Phase III (C)	Carboplatin & Cyclophosphamide	Seems to have inferior OS

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1

21-day cycle for 6 cycles

Variant #7, 100/750

Study	Evidence	Comparator	Efficacy
Kaye et al. 1992	Phase III (E)	Cisplatin & Cyclophosphamide 50/750	Superior OS
McGuire et al. 1996 (GOG 111)	Phase III (E)	Cisplatin & Cyclophosphamide 50/750	Superior 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

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 protocol 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. 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. 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 protocol 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. 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 verified protocol PubMed
6. Kaye SB, Lewis CR, Paul J, Soukop M, Rankin M, Cassidy J, Davis JA, Reed S, MacLean A, Kennedy JH, Symonds RP, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Swapp GA, Sarkar TK, Atkinson RJ, Crawford SM. 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 protocol 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 Organization 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 verified protocol PubMed
9. 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 verified protocol PubMed

Hexa-CAF

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

Regimen

Study	Evidence	Comparator	Efficacy
Young et al. 1978	Phase III (E)	Melphalan	Superior OS
Neijt et al. 1984	Phase III (C)	CHAP-5	Inferior OS

Chemotherapy

• Altretamine (Hexalen)
• Cyclophosphamide (Cytoxan)
• Fluorouracil (5-FU)
• Methotrexate (MTX)

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, Pindeo 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

Second-line therapy

Tamoxifen monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Hurteau et al. 2010 (GOG 198)	Phase III (C)	Thalidomide	Seems not superior

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

Hormonotherapy

• Tamoxifen (Nolvadex)

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

Intraperitoneal therapy

Cisplatin & Cyclophosphamide

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Regimen

Study	Evidence	Comparator	Efficacy
Alberts et al. 1996 (GOG 104)	Phase III (E)	Cisplatin (IV) & Cyclophosphamide	Seems to have superior OS

Chemotherapy

• Cisplatin (Platinol) IP
• Cyclophosphamide (Cytoxan) IV

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