Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer: a Prostate Cancer Clinical Trials Consortium trial.

BACKGROUND: Treatment of high-risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy. METHODS: Eligibility included any of the following: prostate-specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m(2) every 3 weeks for 6 cycles and bevacizumab 15 mg/m(2) every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI. RESULTS: Forty-one patients were treated. Median age was 55 years (range, 40-66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty-eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%-45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%-38%) achieved a >50% post-treatment decline in PSA. Thirty-seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses. CONCLUSIONS: Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials.

Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone.

PURPOSE: Palliation of bone pain can be achieved in men with androgen-independent prostate cancer treated with docetaxel and estramustine (DE) or mitoxantrone and prednisone (MP). While Southwest Oncology Group trial 99-16 demonstrated a survival improvement of DE over MP, the study also was designed to compare the palliation of disease-related symptoms. METHODS: Pain palliation and global quality of life (QOL) were the two primary patient-reported outcomes. Pain was measured with the Present Pain Intensity scale of the McGill Pain Questionnaire-Short Form. The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (QLQ-C30) and its Prostate Cancer Module (PR25) measured QOL and symptom status. Pain and analgesic use were measured at random assignment, every cycle for eight cycles, and 1 year from random assignment; the QLQ-C30 and the PR25 were administered at random assignment, before cycle four (week 10) and cycle eight (month 6) and at 1 year. In addition to the primary intent-to-treat, missing at random analysis, sensitivity analyses were performed to assess robustness of global QOL conclusions under alternative informative missing data assumptions. RESULTS: Six hundred seventy four eligible patients received DE (n = 338) or MP (n = 336). In an intention-to-treat analysis, median overall survival was 17.5 months for the DE arm and 15.6 months for the MP arm (P = .02). There were no statistically significant differences in pain palliation between the treatment arms. The sensitivity analyses showed a consistent lack of statistically significant global QOL differences for the two arms. CONCLUSION: DE had superior clinical efficacy (overall survival, time-to-progression, and prostate-specific antigen declines) with similar global QOL and pain palliation in the MP arm.