Weekly Docetaxel and Bortezomib as First-Line Treatment for Patients with Hormone-Refractory Prostate Cancer: A Minnie Pearl Cancer Research Network Phase II Trial

Abstract Background Docetaxel is currently the standard first-line treatment in patients with hormone-refractory prostate cancer (HRPC). Bortezomib, the first proteasome inhibitor in clinical use, demonstrated activity against prostate cancer in phase I trials. For this reason, we evaluated the efficacy of docetaxel plus bortezomib in the first-line treatment of patients with HRPC. Patients and Methods Between February 2004 and May 2005, 63 eligible patients entered this phase II trial. All patients had metastatic adenocarcinoma of the prostate that had progressed on hormonal therapy. All patients received docetaxel 30 mg/m 2 and bortezomib 1.6 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after 8 weeks of treatment; responding and stable patients continued treatment until tumor progression. Results Sixty patients (95%) received ≤ 2 courses of treatment and were evaluable for response. Fifteen patients (25%; 95% confidence interval, 15%–38%) had a > 50% decrease in serum prostate-specific antigen level with treatment; the median response duration was 8 months. The median progression-free and overall survival times for the entire group were 4.1 months and 13.8 months, respectively; 20% of patients were alive at 2 years. The regimen was well tolerated, with uncommon grade 3/4 toxicity. Conclusion Treatment with this combination of weekly docetaxel and bortezomib showed no suggestion of improved efficacy versus previous results with docetaxel alone. Bortezomib has minimal activity in patients with HRPC and is unlikely to make any impact on treatment efficacy.