Phase II trial of weekly patupilone in patients with castration-resistant prostate cancer.

Abstract

BACKGROUND:

Drug resistance mechanisms can reduce response rate and duration in men with castration-resistant prostate cancer (CRPC) receiving docetaxel-based therapy. Patupilone (epothilone B), a microtubule-targeting agent, may be unaffected by some resistance mechanisms. Therefore, a phase II study assessed the patupilone safety and activity in CRPC patients with and without previous chemotherapy.

METHODS:

CRPC patients received patupilone 2.5 mg/m(2) weekly for 3 weeks of a 4-week cycle. Patients were required to have measurable disease or prostate-specific antigen (PSA) progression (levels>20 ng/ml).

RESULTS:

All 45 enrolled patients (median age, 69 years) were safety and response assessable. Sixty-four percent had previous chemotherapy (55% had previous taxane therapy). Patients received a median of three patupilone cycles. Patupilone was generally well tolerated. Ten (22%) patients experienced grade 3 diarrhea, six (13%) grade 3 fatigue, and one (2%) grade 3 neuropathy with no neutropenia or thrombocytopenia incidence. Six (13%) patients had >or= 50% decline in PSA (three had previous taxane therapy). No patient with measurable disease had a response. Median overall survival was 13.4 months.

CONCLUSIONS:

The safety profile of weekly patupilone in CRPC patients compares favorably with that of other microtubule inhibitors. At the dose and schedule tested, patupilone demonstrated minimal activity in CRPC.

• Authors: A Hussain, R S DiPaola, A D Baron, C S Higano, N S Tchekmedyian, A R Johri
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 20 Issue 3 Pg. 492-7 (Mar 2009) ISSN: 1569-8041 [Electronic] England
• PMID: 19087985 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Epothilones
• epothilone B

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Epothilones (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Orchiectomy
• Prostatic Neoplasms (drug therapy, surgery)