02i7-537<l/H663.00+0 00 0 19fl6 Prrqamrm Prrsi Ltd. A Phase 11 Study of Tamoxifen in Ovarian Cancer MAURICE L. SLEVIN,* VERNON J. HARVEY,* RICHARD J. OSBORNE,* JOHN H. SHEPHERD,? CHRISTOPHER J. WILLIAMSS and GRAHAM M. MEAD: $Department of Medical Oncology and TDepartment of Gynaecologie Oncologie, St Bartholomew k and Hackney Hospitals, London and ZCRC Medical Oncology Unit, Southampton Genera1 Hospital, Southampton, U.K. Abstract-” phase 11 study of tamoxifen was conducted in 22 patients wil stage 111 and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxrfen was administered at a dose of 20 mg twice daily continuously until evidente ofprogression. Twen&one patients had progression of disease within 3 months and one paticnt had stable disease for 6 months. There were no objective responses to this treatment. INTRODUCTION HORMONAL manipulations are of proven value in breast cancer [l], endometrial cancer [2] and prostatic cancer [3] and have been extensively investigated in these tumours. In contrast to the large amount of information available about the hormone sensitivity of these malignancies, little data is available on the response of ovarian cancer to hormonal manipulation. The recent demonstra- tion of oestrogen and progesterone receptors in up to 50% of these tumours [4-71 has suggested a rationale for hormonal manipulation. In addition androgen receptors [8] are common and receptors for follicle stimulation hormone and human chor- ionic gonadotrophin [9] have been found in some tumours. The earliest suggestion that ovarian can- cer might be hormone sensitive resulted from a study using oestrogen (diethylstilboestrol) in pa- tients with advanced disease with 4 out of 14 (28%) patients with advanced disease achieving a partial response [ 101. Subsequently progestogens have been used to treat patients who have failed chemotherapy and the published response rates vary from 0 to 65% [ 111. If the responses in the published literature are reviewed according to World Health Organisation criteria, the mean response is approx. 16% with a range of 0-38% [ 111. Recently it has been suggested that the anti-oestrogen tamoxifen might have therapeutic activity in ovarian cancer [12-141. This phase 11 study was conducted to further evaluate the role of tamoxifen in ovarian malignancy. Accepted 20 September 1985 Correspondence and requests for reprints should be addressed to: Dr. M. L. Slevin, Department of Medical Oncology, St Bartholomew’s Hospital, Londen EClA 7BE, U.K. MATERIALS AND METHODS Patients Twenty-two patients with stage 111 or IV epithe- lial ovarian cancer who had failed to respond to or who had relapsed following cytotoxic chemother- apy were studied. Al1 patients had an histologically proven diagnosis of ovarian carcinoma and al1 had measurable disease. Patients had an estimated life expectancy of at least 3 months. Patients with any evidente of intestinal obstruction were excluded. Patient characteristics are shown in Table 1. Tamoxifen therapy Tamoxifen was administered at a dose of 20 mg twice daily and continued untila there was une- quivocal evidente of progressive disease. RESPONSE Response was assessed by standard World Health Organisation criteria [ 151. RESULTS Twenty-one patients experienced progression of disease within 3 months. In one patient the disease was stable for 6.5 months. NO patient had an objective response to treatment. The median sur- viva1 was 3.5 months with a range of 0.75-12 months. DISCUSSION A number of studies have suggested that tamox- ifen may have activity in ovarian cancer. Myers et al. [ 121 described three patients with advanced recurrent disease who were treated with tamoxifen. One patient achieved a complete response and two 309