A phase II trial of thalidomide, bevacizumab, and docetaxel in patients (pts) with metastatic androgen-independent prostate cancer (AIPC)

Abstract

5114 Background: Angiogenesis plays a vital role in the progression of prostate cancer. Antiangiogenic agents thalidomide (T) and bevacizumab (Bv) may enhance docetaxel (Doc) activity in metastatic AIPC. However, T and Bv have different antiangiogenic mechanisms. Since tumor angiogenesis is a complex interplay of multiple angiogenic factors, we reasoned that combination of mechanistically different antiangiogenic agents T and Bv with Doc might be associated with an adequately high and durable PSA response to merit further study. Methods: Pts are required to have progressive metastatic AIPC and no prior chemotherapy for AIPC. Treatment consists of Doc 75 mg/m2 plus Bv 15 mg/kg day 1, q 21 days as a cycle (C), plus T 200 mg qhs and prednisone 10 mg qd. Enoxaparin is used for thrombosis prevention and pegfilgrastim initiated after detection of grade ≥3 neutropenia. PSA is assayed q C and staging studies are done at C 0, C 2, & then q 3 Cs. Results: 39 pts were enrolled, median age 66 [54–79], Gleason score 8 [74% Gs 10∼8, 26% Gs 7∼6], on-study PSA 92 ng/ml [5.9–4399] and pre-study PSA doubling time 1.6 months [0.3–18.2, 87 % <3 months]. Median treatment Cs is 14 [1- 28]. 34 pts (87%) had PSA declines of ≥50%, with median ≥50% PSA-duration 12 Cs [0∼28]. 3 pts have PSA declines around 40% and 2 stable. 26 pts (67%) had >80% PSA declines. 17 pts with measurable disease were evaluable: 1 CR, 9 PR, & 7 SD, with 59% ORR. Significant toxicities: febrile neutropenia (5/39), syncope (4/39), colon perforation or fistula (2/39), grade 3 bleeding (2/39), thrombosis (2/39). Conclusions: This trial is the first study to combine antiangiogenic agents of different mechanisms with Doc in metastatic AIPC. Most of the accrued patients have unfavorable characteristics as evidenced by a high Gleason score and a short PSA doubling time. However, the combination of T and Bv with Doc appears to result in both a high durable PSA decline rate (87%) and a high response in measurable disease (59%) with acceptable toxicities. No significant financial relationships to disclose.