Skip to main content
NCBI home page
The BMJ logoLink to The BMJ
. 1991 Oct 12;303(6807):884–893. doi: 10.1136/bmj.303.6807.884

Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

PMCID: PMC1671193  PMID: 1834291

Abstract

OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients.

Full text

PDF
884

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aabo K., Hald I., Hørbov S., Dombernowsky P., Hansen H. H., Sørensen H. M., Lundvall F., Nielsen N. C., Sørensen B. L. A randomized study of single agent vs combination chemotherapy in FIGO stages IIB, III and IV ovarian adenocarcinoma. Eur J Cancer Clin Oncol. 1985 Apr;21(4):475–481. doi: 10.1016/0277-5379(85)90040-9. [DOI] [PubMed] [Google Scholar]
  2. Adams M., Johansen K. A., James K. W., Rocker I. A controlled clinical trial in advanced ovarian cancer. Clin Radiol. 1982 Mar;33(2):161–163. doi: 10.1016/s0009-9260(82)80049-4. [DOI] [PubMed] [Google Scholar]
  3. Adams M., Kerby I. J., Rocker I., Evans A., Johansen K., Franks C. R. A comparison of the toxicity and efficacy of cisplatin and carboplatin in advanced ovarian cancer. The Swons Gynaecological Cancer Group. Acta Oncol. 1989;28(1):57–60. doi: 10.3109/02841868909111182. [DOI] [PubMed] [Google Scholar]
  4. Anderson H., Wagstaff J., Crowther D., Swindell R., Lind M. J., McGregor J., Timms M. S., Brown D., Palmer P. Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer. Eur J Cancer Clin Oncol. 1988 Sep;24(9):1471–1479. doi: 10.1016/0277-5379(88)90338-0. [DOI] [PubMed] [Google Scholar]
  5. Aristegui Fernández J., Cisterna Cáncer R., Muñiz Saitua J., Gorostiza E., Pérez Legorburu A., Cos Arregui B., Delgado Rubio A. Prevalencia de infección por el virus de la hepatitis B en instituciones de deficientes mentales. Características epidemiológicas en la provincia de Vizcaya. Med Clin (Barc) 1989 Mar 11;92(9):323–327. [PubMed] [Google Scholar]
  6. Bell D. R., Woods R. L., Levi J. A., Fox R. M., Tattersall M. H. Advanced ovarian cancer: a prospective randomised trial of chlorambucil versus combined cyclophosphamide and cis-diamminedichloroplatinum. Aust N Z J Med. 1982 Jun;12(3):245–249. doi: 10.1111/j.1445-5994.1982.tb02469.x. [DOI] [PubMed] [Google Scholar]
  7. Bolis G., Bortolozzi G., Carinelli G., D'Incalci M., Gramellini F., Morasca L., Mangioni C. Low-dose cyclophosphamide versus adriamycin plus cyclophosphamide in advanced ovarian cancer. A randomized clinical study. Cancer Chemother Pharmacol. 1980;4(2):129–132. doi: 10.1007/BF00254034. [DOI] [PubMed] [Google Scholar]
  8. Brodovsky H. S., Bauer M., Horton J., Elson P. J. Comparison of melphalan with cyclophosphamide, methotrexate, and 5-fluorouracil in patients with ovarian cancer. Cancer. 1984 Feb 15;53(4):844–852. doi: 10.1002/1097-0142(19840215)53:4<844::aid-cncr2820530405>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  9. Bruckner H. W., Pagano M., Falkson G., Creech R., Arseneau J. C., Horton J., Brodovsky H., Davis T. E., Slayton R. W., Greenspan E. Controlled prospective trial of combination chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil for the treatment of advanced ovarian cancer: a preliminary report. Cancer Treat Rep. 1979 Feb;63(2):297–299. [PubMed] [Google Scholar]
  10. Calvert A. H., Newell D. R., Gumbrell L. A., O'Reilly S., Burnell M., Boxall F. E., Siddik Z. H., Judson I. R., Gore M. E., Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748–1756. doi: 10.1200/JCO.1989.7.11.1748. [DOI] [PubMed] [Google Scholar]
  11. Carmo-Pereira J., Costa F. O., Henriques E., Ricardo J. A. Advanced ovarian carcinoma: a prospective and randomized clinical trial of cyclophosphamide versus combination cytotoxic chemotherapy (Hexa-CAF). Cancer. 1981 Nov 1;48(9):1947–1951. doi: 10.1002/1097-0142(19811101)48:9<1947::aid-cncr2820480906>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  12. Carmo-Pereira J., Costa F. O., Henriques E. cis-Platinum, adriamycin, and hexamethylmelamine versus cyclophosphamide in advanced ovarian carcinoma. Cancer Chemother Pharmacol. 1983;10(2):100–103. doi: 10.1007/BF00446218. [DOI] [PubMed] [Google Scholar]
  13. Cohen C. J., Goldberg J. D., Holland J. F., Bruckner H. W., Deppe G., Gusberg S. B., Wallach R. C., Kabakow B., Rodin J. Improved therapy with cisplatin regimens for patients with ovarian carcinoma (FIGO Stages III and IV) as measured by surgical end-staging (second-look operation). Am J Obstet Gynecol. 1983 Apr 15;145(8):955–967. doi: 10.1016/0002-9378(83)90849-9. [DOI] [PubMed] [Google Scholar]
  14. De Palo G. M., De Lena M., Bonadonna G. Adriamycin versus adriamycin plus melphalan in advanced ovarian carcinoma. Cancer Treat Rep. 1977 May-Jun;61(3):355–357. [PubMed] [Google Scholar]
  15. Decker D. G., Fleming T. R., Malkasian G. D., Jr, Webb M. J., Jeffries J. A., Edmonson J. H. Cyclophosphamide plus cis-platinum in combination: treatment program for stage III or IV ovarian carcinoma. Obstet Gynecol. 1982 Oct;60(4):481–487. [PubMed] [Google Scholar]
  16. Delgado G., Smith F. P., McLaughlin E. K., Tuholski N. Single agent vs. combination chemotherapy for ovarian cancer. Am J Clin Oncol. 1985 Feb;8(1):33–37. doi: 10.1097/00000421-198502000-00042. [DOI] [PubMed] [Google Scholar]
  17. Edmonson J. H., McCormack G. M., Wieand H. S., Kugler J. W., Krook J. E., Stanhope C. R., Everson L. K., Laurie J. A., Ebbert L. P., Malkasian G. D. Cyclophosphamide-cisplatin versus cyclophosphamide-carboplatin in stage III-IV ovarian carcinoma: a comparison of equally myelosuppressive regimens. J Natl Cancer Inst. 1989 Oct 4;81(19):1500–1504. doi: 10.1093/jnci/81.19.1500. [DOI] [PubMed] [Google Scholar]
  18. Grönroos M., Nieminen U., Kauppila A., Kauppila O., Saksela E., Väyrynen M. A prospective, randomized, national trial for treatment of ovarian cancer: the role of chemotherapy and external irradiation. Eur J Obstet Gynecol Reprod Biol. 1984 Apr;17(1):33–42. doi: 10.1016/0028-2243(84)90078-9. [DOI] [PubMed] [Google Scholar]
  19. Hubbard S. M., Barkes P., Young R. C. Adriamycin therapy for advanced ovarian carcinoma recurrent after chemotherapy. Cancer Treat Rep. 1978 Sep;62(9):1375–1377. [PubMed] [Google Scholar]
  20. Kato T., Nishimura H., Yamabe T., Terashima Y., Kasamatsu T., Hirabayashi K., Nishiya I., Yajima A., Takamizawa H., Tsutsui F. [Phase III study of carboplatin in ovarian cancer]. Gan To Kagaku Ryoho. 1988 Aug;15(8):2297–2304. [PubMed] [Google Scholar]
  21. Leonard R. C., Smart G. E., Livingstone J. R., Cornbleet M. A., Kerr G. R., Fletcher S., Webb J. N., Smyth J. F. Randomised trial comparing prednimustine with combination chemotherapy in advanced ovarian carcinoma. Cancer Chemother Pharmacol. 1989;23(2):105–110. doi: 10.1007/BF00273526. [DOI] [PubMed] [Google Scholar]
  22. Mangioni C., Bolis G., Pecorelli S., Bragman K., Epis A., Favalli G., Gambino A., Landoni F., Presti M., Torri W. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464–1471. doi: 10.1093/jnci/81.19.1464. [DOI] [PubMed] [Google Scholar]
  23. Marsoni S., Torri W., Taiana A., Gambino A., Grilli R., Liati P., Franzosi M. G., Pistotti V., Parazzini F., Focarile F. Critical review of the quality and development of randomized clinical trials (RCTs) and their influence on the treatment of advanced epithelial ovarian cancer. Ann Oncol. 1990 Sep;1(5):343–350. doi: 10.1093/oxfordjournals.annonc.a057772. [DOI] [PubMed] [Google Scholar]
  24. Masding J., Sarkar T. K., White W. F., Barley V. L., Chawla S. L., Boesen E., Rostom A. Y., Menday A. P. Intravenous treosulfan versus intravenous treosulfan plus cisplatinum in advanced ovarian carcinoma. Br J Obstet Gynaecol. 1990 Apr;97(4):342–351. doi: 10.1111/j.1471-0528.1990.tb01813.x. [DOI] [PubMed] [Google Scholar]
  25. Omura G. A., Bundy B. N., Berek J. S., 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):457–465. doi: 10.1200/JCO.1989.7.4.457. [DOI] [PubMed] [Google Scholar]
  26. Omura G. A., Morrow C. P., Blessing J. A., Miller A., Buchsbaum H. J., Homesley H. D., Leone L. A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma. Cancer. 1983 Mar 1;51(5):783–789. doi: 10.1002/1097-0142(19830301)51:5<783::aid-cncr2820510506>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  27. Omura G., Blessing J. A., Ehrlich C. E., Miller A., Yordan E., Creasman W. T., Homesley H. D. 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):1725–1730. doi: 10.1002/1097-0142(19860501)57:9<1725::aid-cncr2820570903>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  28. Park R. C., Blom J., Disaia P. J., Lagasse L. D., Blessing J. A. 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):2529–2542. doi: 10.1002/1097-0142(19800515)45:10<2529::aid-cncr2820451011>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  29. Parkin D. M., Lärä E., Muir C. S. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988 Feb 15;41(2):184–197. doi: 10.1002/ijc.2910410205. [DOI] [PubMed] [Google Scholar]
  30. Senn H. J., Lei D., Castaño-Almendral A., Brunner K. W., Martz G., Obrecht P., Melchert F., Rhomberg W. Chemo-(Hormon)-Therapie fortgeschrittener Ovarialkarziome der FIGO-Stadien III and IV. Prospektive SAKK-Studie 20/71. Schweiz Med Wochenschr. 1980 Aug 16;110(33):1202–1208. [PubMed] [Google Scholar]
  31. Simes R. J. Publication bias: the case for an international registry of clinical trials. J Clin Oncol. 1986 Oct;4(10):1529–1541. doi: 10.1200/JCO.1986.4.10.1529. [DOI] [PubMed] [Google Scholar]
  32. Tomirotti M., Perrone S., Giè P., Canaletti R., Carpi A., Biasoli R., Lombardi F., Giovanninetti A., Mensi F., Villa S. Cisplatin (P) versus cyclophosphamide, adriamycin and cisplatin (CAP) for stage III-IV epithelial ovarian carcinoma: a prospective randomized trial. Tumori. 1988 Oct 31;74(5):573–577. doi: 10.1177/030089168807400514. [DOI] [PubMed] [Google Scholar]
  33. Tropé C. Melphalan with and without doxorubicin in advanced ovarian cancer. Obstet Gynecol. 1987 Oct;70(4):582–586. [PubMed] [Google Scholar]
  34. Wharton J. T., Edwards C. L., Rutledge F. N. Long-term survival after chemotherapy for advanced epithelial ovarian carcinoma. Am J Obstet Gynecol. 1984 Apr 1;148(7):997–1005. doi: 10.1016/0002-9378(84)90543-x. [DOI] [PubMed] [Google Scholar]
  35. Wilbur D. W., Rentschler R. E., Wagner R. J., Keeney E. D., King A., Hilliard D. A. Randomized trial of the addition of cis-platin (DDP) and/or BCG to cyclophosphamide (CTX) chemotherapy for ovarian carcinoma. J Surg Oncol. 1987 Mar;34(3):165–169. doi: 10.1002/jso.2930340306. [DOI] [PubMed] [Google Scholar]
  36. Williams C. J., Mead G. M., Macbeth F. R., Thompson J., Whitehouse J. M., MacDonald H., Harvey V. J., Slevin M. L., Lister T. A., Shepherd J. H. Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial. J Clin Oncol. 1985 Nov;3(11):1455–1462. doi: 10.1200/JCO.1985.3.11.1455. [DOI] [PubMed] [Google Scholar]
  37. Williams C. J., Stevenson K. E., Buchanan R. B., Whitehouse J. M. Advanced ovarian carcinoma: a pilot study of cis-dichlorodiammineplatinum(II) in combination with adriamycin and cyclophosphamide in previously untreated patients and as a single agent in previously treated patients. Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1745–1753. [PubMed] [Google Scholar]
  38. Wiltshaw E., Evans B., Rustin G., Gilbey E., Baker J., Barker G. A prospective randomized trial comparing high-dose cisplatin with low-dose cisplatin and chlorambucil in advanced ovarian carcinoma. J Clin Oncol. 1986 May;4(5):722–729. doi: 10.1200/JCO.1986.4.5.722. [DOI] [PubMed] [Google Scholar]
  39. Wiltshaw E., Kroner T. Phase II study of cis-dichlorodiammineplatinum(II) (NSC-119875) in advanced adenocarcinoma of the ovary. Cancer Treat Rep. 1976 Jan;60(1):55–60. [PubMed] [Google Scholar]
  40. Young R. C., Chabner B. A., Hubbard S. P., Fisher R. I., Bender R. A., Anderson T., Simon R. M., Canellos G. P., DeVita V. T., Jr Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261–1266. doi: 10.1056/NEJM197812072992301. [DOI] [PubMed] [Google Scholar]
  41. de Oliveira C. F., Lacave A. J., Villani C., Wolff J. P., di Re F., Namer M., Maskens A., George M., Dalesio O., Rotmensz N. Randomized comparison of cyclophosphamide, doxorubicin and cisplatin (CAP) versus cyclophosphamide and doxorubicin (CA) for the treatment of advanced ovarian cancer (ADOVCA). A EORTC Gynecological Cancer Cooperative Group Study. Eur J Gynaecol Oncol. 1990;11(5):323–330. [PubMed] [Google Scholar]
  42. ten Bokkel Huinink W. W., van der Burg M. E., van Oosterom A. T., Neijt J. P., George M., Guastalla J. P., Veenhof C. H., Rotmensz N., Dalesio O., Vermorken J. B. Carboplatin in combination therapy for ovarian cancer. Cancer Treat Rev. 1988 Jun;15 (Suppl B):9–15. doi: 10.1016/0305-7372(88)90030-8. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES