A phase II study of neoadjuvant docetaxel (D) plus bevacizumab (B) in patients (pts) with high-risk localized prostate cancer.

Abstract

4642 Background: Treatment options for high-risk localized prostate cancer remain inadequate, with most pts relapsing despite local therapy. We conducted a phase II multicenter trial of neoadjuvant D +B prior to radical prostatectomy in pts with high-risk localized prostate cancer. Methods: Eligibility included any of the following: PSA >20 ng/mL or PSA velocity >2 ng/mL/yr, cT3 disease, any biopsy Gleason 8–10, Gleason 7 with T3 disease by endorectal (er) MRI. In addition, pts with ≥50% biopsy cores involved and either Gleason 7 or PSA >10 or cT2 disease were eligible. Pts were treated with D 70 mg/m2 q3 weeks x 6 cycles and B 15 mg/m2 q3 weeks x 5 cycles. The primary end point was erMRI partial response (PR, defined as ≥50% decrease in tumor volume) in a single target lesion after chemotherapy. Results: 42 pts were enrolled, and 41 were treated. Median age was 55 yrs (range, 40–66 yrs). Baseline characteristics included: median PSA 10.1 ng/mL (range, 2.1–72.4 ng/mL), cT2 49%, cT3 32%, and Gleason 8–10 73%. Thirty-eight of 41 (93%) pts completed all 6 cycles. Grade ≥ 3 adverse events included hyperglycemia (1/41), allergic reaction (1/41), cough, lymphopenia (3/41), and febrile neutropenia (3/41). Thirty-seven of the 41 pts underwent radical prostatectomy. Reasons for not proceeding with surgery included: a bladder neck injury, positive lymph nodes, and withdrawal of consent in 2 pts. Response data are shown in the Table. No pts achieved a complete pathologic response. Conclusions: Neoadjuvant D+B demonstrates clinical activity in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in solid tumors in general, requires further elucidation through ongoing and planned randomized trials. Response assessments. Outcome measure Number (%) erMRI partial response 12/41 (29%) Any PSA decline 31/41 (76%) > 50% PSA decline 9/41 (22%) Pathologic downstaging 14/41 (34%) Pathologic node positive 8/41 (20%) Positive margins 14/41 (34%) Extracapsular extension 23/41 (56%) Seminal vesicle involvement 12/41 (29%)