Combination therapy may benefit refractory prostate cancer patients

Researchers have reported positive preliminary results from a phase II study of AT-101 in combination with docetaxel (Taxotere) and prednisone in men with docetaxel-refractory, castrate-resistant prostate cancer.

AT-101 is an oral, pan-Bcl-2 inhibitor currently in double-blind, randomized phase II clinical trials.

Initial findings from the ongoing open label, multicenter study demonstrates that AT-101 can be administered safely with docetaxel/prednisone in docetaxel-refractory, castrate-resistant patients. Investigators also observed clinical responses, based on both PSA and Response Evaluation Criteria In Solid Tumors (RECIST), including four patients with a confirmed partial response, as reported at the 2009 Genitourinary Cancers Symposium in Orlando, FL.

The study included data from 37 men with docetaxel-refractory castrate-resistant prostate cancer who were treated with docetaxel (75 mg/m2 every 3 weeks), prednisone (5 mg twice on days 1-21), and AT-101 (40 mg twice on days 1-3 of each 21-day cycle). Safety and efficacy were assessed at 3-week intervals, with radiologic assessments performed at 6-week intervals for patients with soft tissue disease and bone scans performed after cycle 6 and at completion of therapy. Ten of the 37 patients remain on study.

Fourteen of 37 treated patients (38%) had at least a 30% decrease in PSA level, and seven (19%) achieved a confirmed partial response. Twenty patients had measurable disease, five of whom (25%) had a partial response by RECIST, with additional patients eligible to achieve a response. Four patients have been on therapy for 6 months or more.

“This first look at the data is very encouraging, particularly since all of these patients were truly refractory to docetaxel, having not simply failed to respond but actually experienced disease progression during prior therapy,” said lead author James Reeves, MD, of Florida Cancer Specialists. “Our results to date suggest that stimulating cancer cell apoptosis through Bcl-2 pathways with AT-101 may in fact extend the clinical utility of docetaxel in this cohort of highly treatment-resistant patients.”

Look for additional coverage of the Genitourinary Cancers Symposium in an upcoming issue of Urology Times.