Dr. Yang-Min Ning and collaborators reported, in the April 20, 2010 issue of the Journal of Clinical Oncology, a Phase II trial which combined chemotherapy (docetaxel) with an anti-angiogenesis drug for men with castration-resistant prostate cancer (CRPC). The data suggests that such a combination is more effective than chemotherapy alone.
The studies used the standard chemotherapy for CRPC, docetaxel. The two anti-angiogenesis drugs that were used were thalidomide and bevacizumab (Avastin). Thalidomide and bevacizumab are both anti-angiogenesis drugs that stop or slow down the growth of blood vesicles that feed tumors. However, the drugs use different mechanism to inhibit the growth of the supporting blood vesicles. The investigators hypothesized that the combination of these drugs would have an additive effect when used with docetaxel.
Among the 60 men enrolled in the single arm (all three drugs combined) phase II study Six (6) men remained on study at the time of this report. Of the remaining 54 men, 41 had disease progression, 5 withdrew secondary to toxicity, 7 withdrew voluntarily and one died of other causes. The majority of men required some dose modifications and all had grade 3 or 4 toxicities, primarily, neutropenia.
*Of the 58 patients with PSA active disease, 52 (89.6%) had a PSA decline >50%, 4 had PSA decline <50%, 2 had a rising PSA while on study, 44 (76%) had PSA decline >75%, and 51 (87.9%) had PSA decline >30% in the first three months of treatment.
*Confirmed responses included two complete and 19 partial responses. The overall response rate was 64%. Eleven men had stable disease and one had disease progression.
*As a secondary endpoint, progression free survival was measured and the median time to progression was 18.3 months. The median survival time for the three-drug combination was 28.2 months, while their predicted survival was 14 months.
*Men with a PSA decline >75% had a significant increase in circulating apoptotic endothelial cells compared with those who had a <75% PSA decline, indicating greater anti-angiogenic activity.The combination of bevacizumab, thalidomide, and docetaxel has demonstrated a very clear positive effect. Additional confirmation studies should be immediately carried out using this combination of drugs. This combination could quickly become standard of care since all the drugs have already been approved by the FDA for other purposes.J Clin Oncol. 2010 Apr 20;28(12):2070-6 10.1200/JCO.2009.25.4524; Ning YM, Gulley JL, Arlen PM, Woo S, Steinberg SM, Wright JJ, Parnes HL, Trepel JB, Lee MJ, Kim YS, Sun H, Madan RA, Latham L, Jones E, Chen CC, Figg WD, Dahut WLPubMed Abstract PMID: 20308663Joel T Nowak, MA, MSW