Technical Report Abstracts
The outlook for patients with advanced ovarian cancer who experience disease relapse following treatment with platinumbased chemotherapy is poor. As well as searching for more effective cytotoxic chemotherapy regimens recent attention has also focused on identifying those agents which have minimal toxicity but still retain clinical activity. In response to the discovery of oestrogen and progesterone receptors on ovarian cancer cells (Holt et al., 1979; Rendina et al., 1982; Ford et al., 1983; Willocks et al., 1983) hormonal therapy with either tamoxifen or progestagins has been undertaken by many investigators. However to date therapeutic results have been disappointing with response rates to tamoxifen ranging from 0% to 10% (Shirey et al., 1985; Slevin et al., 1986; Weiner et al., 1987; Osborne et al., 1988) and response rates to various progestagins ranging from 0% to 20% (Slotman & Rao, 1988). Androgen receptors have now also been identified on ovarian cancer cells (Hamilton et al., 1981) suggesting that therapy with androgen antagonists may have therapeutic potential. Cyproterone acetate is a steroidal antiandrogen which blocks the androgen receptor but in addition has potent progestational and antigonadotropic effects (Neumann, 1982). In 1989 Alma et al. reported that culture of an ovarian cancer cell line exhibiting androgen receptors with 10-5 M cyproterone acetate for 24 h resulted in the accumulation of 94% of cells in the GO/GI phase of the cell cycle. The same investigators also reported the effect of cyproterone acetate 150 mg per day for 1 week in five patients with advanced ovarian cancer in relapse after several chemotherapy regimens including cisplatin. Tumour proliferative activity as assessed by the thymidine labelling index of malignant ascitic cells was assessed prior to and following the 1 week of therapy. All patients showed a reduction in thymidine labelling index with post treatment values ranging from 40% to 80% of pretreatment values suggesting that cyproterone may at least have some cytostatic effect in vivo. However to date there are no clinical studies reporting the outcome of long term therapy and the current study was designed to further assess the therapeutic potential of cyproterone acetate in refractory ovarian cancer patients. Fifty-six patients with advanced ovarian cancer either refractory to or relapsing after platinum-based chemotherapy and with a life expectancy of greater than 2 months were treated. In addition six patients considered too frail for platinum-based chemotherapy were also treated. Standard WHO criteria were used to assess response and toxicity. Only patients with no radiological change in assessable disease were classified as static disease. Patients with overt or incipient bowel obstruction or with renal failure were excluded from the study. Table I demonstrates the patient and tumour characteristics. Treatment consisted of continuous oral cyproterone acetate 100 mg three times daily. Treatment was only stopped for progression of disease or toxicity. The median duration of treatment was 10 weeks. Details of tumour response and durations of response or static disease status are summarised in Table II. Fifty-eight patients are evaluable for response. Four patients (6.8%), all with serous or mucinous cystadenocarcinomas, experienced partial responses (PR) for 2.5, 3, 17 + and 18 + months. Two of the four responding patients had not received prior platinum-containing chemotherapy due to frailty. One of these received cyproterone acetate immediately after progressing on chlorambucil and the other had also progressed on chlorambucil having had a complete remission of disease on chlorambucil 3 years earlier. Of the other two responding patients one, who achieved a PR for 17 + months, was treated immediately after failing to respond to carboplatin having experienced a complete remission on cisplatin 5 years previously. The other, who achieved a PR for 18 + months, was in relapse 2.5 years after achieving a complete remission with cisplatin. In addition two of seven patients with well differentiated tumours responded compared to one of 25 and 0 of 22 patients with moderately and poorly differentiated tumours respectively. In the other responding patient tumour grade was unknown. A further eight patients (13.8%) demonstrated static disease (SD) for 2 to 11 months before experiencing further