Vinflunine (VFL) as salvage chemotherapy in hormone-refractory prostate cancer (HRPC)

Abstract

16059 Background: Two randomized, phase III trials have demonstrated survival benefits for docetaxel-based chemotherapy in patients (pts) with HRPC. Though some pts retain sensitivity to this agent after completion of therapy, progression of their disease eventually occurs. To date, there is no second-line therapy with proven survival benefits. VFL is a novel vinca alkaloid with demonstrated preclinical antitumor activity in prostate cancer models, and clinical activity in several solid tumors including breast and bladder cancer. In this multicenter phase II trial, we evaluated VFL as salvage chemotherapy in HRPC. Methods: Eligibility criteria: progressive hormone-refractory metastatic or incurable localized prostate carcinoma; ECOG PS 0–2; prior docetaxel; ≤ 2 prior chemotherapy regimens; no prior anthracycline; adequate bone marrow, kidney and liver function; informed consent. All pts received: VFL 320 mg/m2 IV every 3 weeks (280 mg/m2 for pts ECOG PS 2, GFR < 60 cc/min, or prior pelvic RT). Pts were reevaluated after 2 cycles (6 weeks); responding/stable pts received 6 cycles. This study was designed to detect a response rate > 15%; 4 responses in the first 26 evaluable pts were necessary to proceed to the second stage. Results: Between May 2007 and November 2007, 35 pts were enrolled: median age, 75 years (range 52–86); ECOG 0/1/2, 6/26/3 pts; bone metastases, 33 pts (94%); measurable disease, 14 pts (40%); > 1 prior chemotherapy regimen, 23 pts (66%). Pts received VFL for a mean of 2.6 cycles (range 1–6). 27 pts were evaluable for PSA response: 1 pt had a partial response (4%), 9 pts (33%) had stable disease, and 17 pts (63%) had progression. The single PSA responder also had an objective PR. Eight pts were inevaluable (too early, 6; withdrew from study for personal reasons, 2). Most patients progressed rapidly; only 32% were progression-free at 3 months. Grade 3/4 toxicities included neutropenia (40%), fatigue (14%), dehydration (11%), anemia (9%), and abdominal pain/cramping (6%). No treatment-related deaths occurred. Conclusions: VFL has minimal activity in heavily pretreated pts with HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, sanofi-aventis, SCRI