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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: An exact evaluation of the role of high-dose estrogens requires additional investigation.