Summary
After stratification according to diameter of the largest residual tumor, 120 previously untreated ovarian cancer patients were randomized to receive adriamycin and cyclophosphamide in combination with hexamethylmelamine (HAC) or cis-dichlorodiamineplatinum (PAC). The surgical response rates were 66% to HAC and 70% to PAC, with median times to progression of 14 and 22 months and median survival times of 23 and 24 months, respectively. In patients with residual tumor >2 cm the surgical response rates to HAC and PAC were 56% and 63%, with complete response rates of 13% and 21%, respectively. In two of five complete responders to HAC there has still been no progression at 38 and 48 months, with a median response duration of 25 months. Only one of the nine complete responders to PAC has relapsed, at 33 months, while in the eight others response is maintained at follow-up times of 35–64 months. Myelosuppression was generally mild and similar in the two arms. No significant nonhematological toxicity was reported. It is concluded that at a median follow-up time of 36 months HAC is as effective as PAC in terms of response, duration of remission, and survival in previously untreated advanced ovarian cancer.
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Barker GH, Wiltshaw E (1981) Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Lancet I:747–750
Bolis G, Bortolozzi G, Carinelli G et al. (1980) Low-dose cyclophosphamide versus adriamycin plus cyclophosphamide in advanced ovarian cancer. A randomized clinical study. Cancer Chemother Pharmacol 4:129–132
Bruckner HW, Cohen CJ, Kabakov B, et al. (1977) Combination chemotherapy of ovarian carcinoma with platinum: Improved therapeutic index. Proc Am Assoc Cancer Res 18:339
Bruckner HW, Cohen CJ, Goldberg J et al. (1983) Ovarian cancer: comparison of adriamycin and cisplatin ± cyclophosphamide. Proc Am Soc Clin Oncol 2:152
Day TG Jr, Gallager HS, Rutledge FN (1975) Epithelial carcinoma of the ovary: prognostic importance of histologic grade. Natl Cancer Inst Monogr 42:15–18
Edmonson JH, Fleming TR, Decker DG, et al. (1979) Different chemotherapeutic sensitivities and host factors affecting prognosis in advanced ovarian carcinoma versus minimal residual disease. Cancer Treat Rep 63:241–247
Edwards CL, Herson J, Gershenson DM, et al. (1983) A prospective randomized clinical trial of melphalan and cis-platinum versus hexamethylmelamine adriamycin and cyclophosphamide in advanced ovarian cancer. Gynecol Oncol 15:261–277
Ehrlich CE, Einhorn L, Williams SD, et al. (1979) Chemotherapy for stage III–IV epithelial ovarian cancer with cis-dichlorodiammineplatinum (II), adriamycin, and cyclophosphamide: A preliminary report. Cancer Treat Rep 63:281–288
Greco FA, Julian CG, Richardson RL, et al. (1981) Advanced ovarian cancer: Brief intensive combination chemotherapy and second-look operation. Obstet Gynecol 58:199–205
Griffiths CT, Parker LM, Fuller AF Jr (1979) Role of cytoreductive surgical treatment in the management of advanced ovarian cancer. Cancer Treat Rep 63:235–240
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Statist Assoc 53:457–481
Lloyd RE, Jones SE, Salmon SE, et al. (1976) Combination chemotherapy with adriamycin (NSC-123127) and cyclophosphamide (NSC-26271) for solid tumors: A phase II trial. Cancer Treat Rep 60:77–83
Ozols RF, Garvin AJ, Costa J et al. (1979) Histologic grade in advanced ovarian cancer. Cancer Treat Rep 63:255–263
Peto R, Pike MC, Armitage P, et al. (1977) Design and analysis of randomised clinical trials requiring prolonged observation of each patient: II. Analysis and examples. Br J Cancer 35:1–39
Piver MS, Lele S, Barlow JJ (1981) Cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAP) as second-line chemotherapy for ovarian adenocarcinoma. Cancer Treat Rep 65:149–151
Raju KS, McKinna JA, Barker GH et al. (1982) Second-look operations in the planned management of advanced ovarian carcinoma. Am J Obsted Gynecol 15:650–654
Schwartz PE, Smith JP (1980) Second-look operations in ovarian cancer. Am J Obsted Gynecol 138:1124–1130
Sessa C, D'Incalci M, Valente I et al. (1982) Hexamethylmelamine. CAF (cyclophosphamide, methotrexate and 5-FU) and cis-platin-CAF in refractory ovarian cancer. Cancer Treat Rep 66:1233–1234
Smith JP, Delgado G, Rutledge F, (1976) Second-look operation in ovarian carcinoma. Postchemotherapy. Cancer 38:1438–1442
Stehman FB, Ehrlich CE, Einhorn LH et al. (1983) Long-term follow-up and survival in stage III–IV epithelial ovarian cancer treated with cis-dichlorodiammine platinum, adriamycin and cyclophosphamide (PAC). Proc Am Soc Clin Oncol 2:147
Wharton JT, Herson Y (1981) Surgery for common epithelial tumors of the ovary. Cancer 48:582–589
Wiltshaw E, Kroner T (1976) Phase II study of cis-dichlorodiamineplatinum (NSC-119875) in advanced adenocarcinoma of the ovary. Cancer Treat Rep 60:55–60
Woodman RJ, Sirica AE, Gang M, et al. (1973) The enhanced therapeutic effect of cis-platinum diamminodichloride (II) against L1210 leukemia when combined with cyclophosphamide or 1,2,bis(3,5-dioxopiperazine-1-yl)propane or several other antitumor agents. Chemotherapy 18:169–183
Young RC (1975) Chemotherapy of ovarian cancer: Past and present. Semin Oncol 2:267–276
Young RC, Chabner BA, Hubbard SP, et al. (1978) Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med 299:1261–1266
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Part of the work reported in this paper has already been presented at the AACR Meetings in 1980 in San Diego (Proc Am Assoc Cancer Res 21: 148, Abs. 595) and in 1981 in Washington DC (Proc Am Assoc Cancer Res 22: 166 Abs. 660)
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Sessa, C., Bolis, G., Colombo, N. et al. Hexamethylmelamine, adriamycin, and cyclophosphamide (HAC) versus cis-dichlorodiamineplatinum, adriamycin, and cyclophosphamide (PAC) in advanced ovarian cancer: A randomized clinical trial. Cancer Chemother. Pharmacol. 14, 222–228 (1985). https://doi.org/10.1007/BF00258120
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DOI: https://doi.org/10.1007/BF00258120