[High dose fosfestrol in phase I-II trial for the treatment of hormone-resistant prostatic adenocarcinoma].

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer, independently of palliative radiotherapy. The evolution to hormone-resistance status leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol diphosphate) has been suggested to circumvent hormone-resistance and to induce a direct cytotoxic effect. Sixteen patients with hormone-resistant prostate cancer were treated by continuous infusion of high-dose fosfestrol according to two schedules: 10 patients were included in a phase I trial of a daily escalating dose from 1.5 g/d to 4.5 g/d for 7 to 10 days. Six other patients were uniformly treated by 4 g/d for 3.5 h for 5 days. Between each course, patients received orally 300 mg/d fosfestrol and 200 mg/d salicylic acid. The mean age was 65 years (range 51-75). Mean number of courses was two (extremes 1-7). Toxicities: reversible weight gain was observed in five patients. One patient presented a pulmonary edema which was resolved immediately after diuretics. One patient and 9 patients respectively experienced grade III and II (OMS) nausea and vomiting. Transient perineal pruritus occurred in 5 patients. Responses: 15 patients were evaluable (one early death occurred on day 3 from tumor progression complicated by an intravascular coagulation disease). There were four objective stabilizations (NPCP criteria) lasting 2 m, 2 m, 5 m and 10 m respectively. Subjective improvement of pain was observed in five other patients. There was more than 50% reduction of PSA in eight patients. High-dose fosfestrol seems to have some objective activity with moderate toxicity and warrants further investigation.