Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration.

Abstract

BACKGROUND:

Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer.

PATIENTS AND METHODS:

Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks.

RESULTS:

Thirteen patients were treated at two dose levels (35 and 40 mg/m(2)). Three of six patients treated at 40 mg/m(2) developed grade 4 neutropenia, establishing 35 mg/m(2) as the maximum-tolerated dose. Significant peripheral neuropathy (grade >/= 2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of >/= 50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%).

CONCLUSIONS:

The phase II dose of BMS-247550 combined with EMP is 35 mg/m(2) over 3 h every 3 weeks. This combination is safe and >/= 50% post-therapy declines in PSA were seen in 11 of 12 patients (92%).

• Authors: O Smaletz, M Galsky, H I Scher, A DeLaCruz, S F Slovin, M J Morris, D B Solit, U Davar, L Schwartz, W K Kelly
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 14 Issue 10 Pg. 1518-24 (Oct 2003) ISSN: 0923-7534 [Print] England
• PMID: 14504052 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Hormonal
• Epothilones
• Estramustine
• Prostate-Specific Antigen
• ixabepilone
• epothilone B

Topics

• Adenocarcinoma (drug therapy, secondary)
• Adult
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacology)
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects, pharmacology)
• Bone Neoplasms (secondary)
• Castration
• Dose-Response Relationship, Drug
• Epothilones (administration & dosage, adverse effects, pharmacology)
• Estramustine (administration & dosage, adverse effects, pharmacology)
• Humans
• Male
• Maximum Tolerated Dose
• Microtubules (drug effects)
• Middle Aged
• Prostate-Specific Antigen (analysis)
• Prostatic Neoplasms (drug therapy)
• Treatment Outcome