Clinical implication of medroxyprogesterone acetate against advanced ovarian carcinoma: a pilot study

Purpose of investigation: The present study was performed to identify the effects of medroxyprogesterone acetate (MPA) plus adjuvant chemotherapy on advanced epithelial ovarian carcinoma (FIGO Stage III/IV). Methods: A total of 50 patients were enrolled in this study. A relatively low dose of MPA (200 mg/day) after surgery was administered in combination with platinum-based chemotherapy and the treatment was continued for two years. Patients' backgrounds were also analyzed. Results: Relapse-free survival (p < 0.05) and overall survival (p < 0.001) rates in FIGO Stage III/IV ovarian cancer patients with MPA combined chemotherapy were significantly longer than the control group. The effect was more prominent in the higher progesterone receptor expression Group. The chemotherapy regimens (cyclophosphamide, doxorubicin and cisplatin vs paraplatin plus cyclophosphamide or paclitaxel) did not affect prognosis. Conclusion: MPA with platinum-based chemotherapy as an adjuvant therapy might improve the prognosis in FIGO Stage III/IV epithelial ovarian cancer cases. A randomized controlled study is still needed for further analyses.

Medroxyprogesterone acetate; Progesterone receptor; Ovarian cancer; Survival

[1] Tamakoshi K., Kondo T., Yasuya H., Hori Y., Kikkawa F., Toyoshima H.: “Trends in the mortality (1950-70) and incidence (1975-1993) of malignant ovarian neoplasm among Japanese women: analses by age, time, and birth cohort”. Gynecol. Oncol., 2001, 83, 64.

[2] Warwick J., Kehoe S., Earl H., Luesly D., Redman R., Chan K.K.,: “Long-term follow-up of patients with advanced ovarian cancer treated in randomized clinical trials”. Br. J. Cancer, 1995, 72, 1513.

[3] The 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, 360, 505.

[4] Adami H.O., Hsieh C.C., Lambe M., Trichopoulos D., Leon D., Persson I. et al.: “Parity, age at first childbirth, and risk of ovarian cancer”. Lancet, 1994, 344, 1250.

[5] La Vecchia C., Franceschi S.: “Oral contraceptive and ovarian cancer”. Eur. J. Cancer Prev., 1999, 8, 297.

[6] Longcope C.: “Endocrine function of the postmenopausal ovary”. J. Soc. Gynecol. Invest., 2001, 8, S67.

[7] Wimalasena J., Meehan D., Cavallo C.: “Human epithelial ovarian cancer cell steroid secretion and its control by gonadotropins”. Gynecol. Oncol., 1991, 41, 56.

[8] Bu S.Z., Yin D.L., Ren X.H., Jiang L.Z., Wu Z.J., Gao Q.R. et al.: “Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines”. Cancer, 1997, 79, 1944.

[9] Rodriguez G.C., Walmer D.K., Cline M.: “Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis?”. J. Soc. Gynecol. Invest., 1998, 5, 271.

[10] Hempling R.E., Piver M.S., Eltabbakh G.H., Recio F.O.: “Progesterone receptor status is a significant prognostic variable of progression- free survival in advanced epithelial ovarian cancer”. Am. J. Clin. Oncol., 1998, 21, 447.

[11] Piver M.S., Barlow J.J., Lauin J.R., Blumenson L.E.: “Medroxyprogesterone acetate versus hydroxyprogesterone caproate in women with metastatic endometrial adenocarcinoma”. Am. J. Clin. Oncol., 1980, 45, 268.

[12] Ver Der Vange N., Greggi S., Burger C.W., Kenemans P., Vermorken J.B.: “Experience with hormonal therapy in advanced epithelial ovarian cancer”. Acta. Oncol., 1995, 34, 810.

[13] Thigpen J.T., Brady M.F., Alvarez R.D., Adelson M.D., Homesley H.D., Manetta A., et al.: “Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose response study by the Gynecologic Oncology Group”. J. Clin. Oncol., 1999, 17, 1736.

[14] Bonte J., Janssens J.P., Ide P.: “Modalities and results of a combined anti-estrogenic therapy by means of tamoxifen and medroxyprogesterone in gynecologic cancerlogy”. Eur. J. Gynecol. Oncol., 1986, 7, 45.

[15] Serow S.F., Scully R.E., Sobin L.H.: “International classification of tumors. Histological typing of ovarian tumours”. WHO, Geneva, 1973, 37.

[16] Krajewska M., Fenoglio-Preiser C.M., Krajewski S., Song K., Macdonald J.S., Stemmerman G. et al.: “Immunohistochemical analysis of Bcl-2 family proteins in adenocarcinoma of the stomach”. Am. J. Pathol., 1996, 149, 1449.

[17] Mallick S., Horwitz S.B.: “A role for progesterone in multi-drug resistance”. In: Parlik E.J. (ed.) Estrogens, Progestins, and Their Antagonists. Boston, Birkhauser, 1996, 123.

[18] Yamamoto T., Terada N., Nishizawa Y., Petrow V.: “Angiostastic activities of medroxyprogestrerone acetate and its analogues”. Int. J. Cancer, 1994, 56, 393.

[19] Kammerman S., Demopoulos X.Y., Raphael C., Ross J.: “Gonadotropic hormone binding to human ovarian tumors”. Hum. Pathol., 1981, 12 (suppl.), 886.

[20] Zaucha R., Sosinska-Mielcarek K., Jassem J.: “Long-term survival of a patient with primarily chemo-resistant metastatic cancer treated with medroxyprogesterone acetate”. Breast, 2004, 13, 321.

[21] Simons J.P., Aaronson N.K., Vansteenkiste J.F., ten Velde G.P, Muller M.J. et al.: “Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage nonhormone-sensitive cancer: a placebo-controlled multicenter study”. J. Clin. Oncol., 1996, 14, 1077.