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.
Droz
J P
JP
Department of Medicine, Institut Gustave-Roussy, Villejuif, France.
Kattan
J
J
Bonnay
M
M
Chraibi
Y
Y
Bekradda
M
M
Culine
S
S
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004351:Drug Resistance; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004054:Diethylstilbestrol; C004955:fosfestrol