Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the prostate.

Abstract

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

• Authors: J P Droz, E De Smedt, J Kattan, F Keuppens, S Khoury, C Mahler, L Denis
• Journal: The Prostate (Prostate) Vol. 24 Issue 2 Pg. 62-6 ( 1994) ISSN: 0270-4137 [Print] United States
• PMID: 7508621 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Diethylstilbestrol
• fosfestrol
• Acid Phosphatase
• Prostate-Specific Antigen

Topics

• Acid Phosphatase (analysis)
• Adenocarcinoma (drug therapy, pathology, secondary, surgery)
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Biomarkers, Tumor (analysis)
• Bone Neoplasms (secondary)
• Combined Modality Therapy
• Diethylstilbestrol (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Drug Resistance
• Humans
• Infusions, Intravenous
• Lung Neoplasms (secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Orchiectomy
• Prostate (drug effects, enzymology, immunology)
• Prostate-Specific Antigen (analysis)
• Prostatic Neoplasms (drug therapy, pathology, surgery)