Clinical outcome of taxane-resistant (TR) hormone refractory prostate cancer (HRPC) patients (pts) treated with subsequent chemotherapy (ixabepilone (Ix) or mitoxantrone/prednisone (MP)

Abstract

4558 Background: The clinical course of TR HRPC pts has not previously been evaluated in a large, prospective study. No standard treatment exists for this pt population, although MP is frequently used. Ix is an epothilone B analogue with activity against TR cell lines. Methods: Metastatic HRPC pts with disease progression during or within 60 days of stopping T chemotherapy were eligible. In a 2-arm, non-comparative randomized phase II study, pts were assigned to receive either: 1) M 14 mg/m2 IV q3wks and P 5 mg PO BID or 2) I × 35 mg/m2 IV q3wks. Crossover was allowed for progression or toxicity. The study’s primary endpoint was to detect a ≥ 50% PSA decline by Consensus Criteria in at least 25% of 2nd-line pts (H0 = 10%, α = 0.04, β = 0.18 for each arm). Pts were followed for survival. Results: Forty-one evaluable pts each were accrued to Ix and to MP. The median follow-up is 5.0 months (range: 0.3–19.5). The median number of cycles administered to each 2nd-line arm is 3 (range: Ix: 1–8, MP: 1–12). Median survival from protocol entry is 13.0 months with Ix and 12.5 months with MP. Confirmed 2nd-line post-therapy (rx) ≥50% PSA declines were observed in 17% of Ix pts (95% CI = 7–32) and 20% of MP pts (95% CI = 9–35). Of pts with measurable disease, partial responses were observed in 1/18 pts on 2nd-line Ix (6%; 95% CI = 0.1–27.3) and in 1/15 pts on 2nd-line MP (7%; 95% CI = 0.2–31.9). Median duration on 2nd-line Ix and MP was 2.2 months and 2.3 months, respectively. Crossover to 3rd-line rx occurred in 39% of Ix pts and 68% of MP pts. Confirmed 3rd-line post-rx ≥50% PSA declines were observed in 3/24 Ix pts and in 4/13 MP pts. The most common grade 3/4 toxicity associated with 2nd-line rx was neutropenia as previously reported (41% of Ix pts, 54% of MP pts). Conclusions: This prospective trial has characterized TR HRPC pts as having an observed median survival of approximately 1 year. This may be a useful reference for the screening of effective agents in the 2nd-line setting for TR HRPC. Both Ix and MP appear to have only modest activity as 2nd- and 3rd-line rx in this highly selected TR HRPC population. This study was supported by Bristol-Myers Squibb and the Prostate Cancer Foundation. No significant financial relationships to disclose.