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Addition of bevacizumab, thalidomide to docetaxel, prednisone shows promise in midstage prostate cancer trial

Tuesday, May 04 2010 | Comments

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What's This? In men with metastatic castration-resistant prostate cancer, the combination of bevacizumab and thalidomide plus docetaxel and prednisone doubled overall survival time relative to the survival time predicted for this patient population, according to data from a recently published study.

Angiogenesis is linked to progression in prostate cancer and is inversely associated with survival, the authors explained. Two antiangiogenic drugs, thalidomide and bevacizumab, have different mechanisms of action, which have led some researchers to hypothesize that combining them with docetaxel and prednisone would be beneficial, they added.

To test this hypothesis, the investigators initially conducted a mouse study comparing the efficacy of various combinations of bevacizumab, thalidomide, and docetaxel and found that the combination of the two antiangiogenic agents and docetaxel reduced tumor volume the most as compared with docetaxel alone or docetaxel plus either one of the antiangiogenic agents.

These results provided the impetus to initiate an open-label Phase II study in 60 men with progressive metastatic castration-resistant prostate cancer, 2 of whom did not have measurable prostate-specific antigen (PSA) activity. All patients received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone.

PSA decline of >=50% was the primary endpoint. Time to progression, overall survival, and safety were secondary endpoints.

PSA declines of >=50% were measured in 52 of the 58 patients with measurable PSA activity at baseline (89.6%; 95% CI, 78.8%-96.1%). There were 2 confirmed complete responses and 19 confirmed partial responses among the 33 patients with measurable disease (measurable disease was based on Response Evaluation Criteria in Solid Tumors). The overall response rate was 64%.

Estimated median disease-free survival reached 18.3 months.

After a median potential follow-up of 34 months, 38 of 60 patients (63%) died. From study entry, the median survival was 28.2 months. The predicted median survival for this patient population--based on the Halabi nomogram--was approximately 14 months.

The investigators noted that the estimated survival might increase with longer follow-up, because only 38 deaths were included in the analysis and most patients remaining alive are 18 to 36 months from their on-study dates.

Although all of the patients developed grade III/IV neutropenia, the investigators said the combination was "generally well-tolerated in most patients with expected and manageable toxicities observed."

"[T]he impressive response rate for this treatment warrants definitive evaluation. The high response rate was accompanied by an encouraging estimated median survival rate in this patient population," the authors said. "This warrants further studies of multiple antiangiogenic agents with different acting mechanisms combined with docetaxel." (Ning Y-M, et al. J Clin Oncol 2010;28:2070-2076.)

This information concerns a use that has not been approved by the Food and Drug Administration.

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