High-dose continuous-infusion fosfestrol in hormone-resistant prostate cancer

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Abstract
The initial treatment of advanced-stage prostate cancer is total androgen deprivation. Autonomous proliferation of primarily or secondarily hormonal unresponsive cells may explain the development of hormone-refractory status. The median survival of patients with hormone-resistant disease is short; there is no standard regimen of chemotherapy. Fosfestrol or diethylstilbestrol diphosphate and its metabolites have cytotoxic activity in hormone-refractory prostatic cell lines. Pharmacokinetic studies have shown that fosfestrol metabolites have a short half-life that supports the use of long-term infusion in the clinic. A review of the literature shows that high-dose fosfestrol induces no objective response, a greater than 50% tumor marker decrease in 50% of patients, a subjective improvement in 75% of patients, and cardiovascular complications in 5% of patients. The median survival time of patients is 5 months after the onset of treatment. An exact evaluation of the role of high-dose estrogens requires additional investigation.