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.