Combination angiogenesis inhibition can be safely administered with appropriate supportive measures and potentially provide clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC), a study published online ahead of print in BJU International has shown.1
Because preclinical data have demonstrated the significance of angiogenesis in prostate cancer, previous clinical trials have assessed using angiogenesis inhibitors in combination with docetaxel, but with limited success. Therefore, researchers sought to evaluate multiple antiangiogenic therapies together as a means to reduce resistance and optimize this therapeutic strategy.
For the open-label, phase 2 trial, researchers enrolled 63 patients with mCRPC. All patients received docetaxel 75 mg/m2 intravenously and bevacizumab 15 mg/kg intravenously on day 1 of each 21-day cycle, in combination with dose-escalated lenalidomide and prednisone 10 mg daily. Patients also received supportive measures including prophylactic pegfilgrastim and enoxaparin.
Results showed that of the 61 evaluable patients, 93%, 90%, and 54% had prostate-specific antigen (PSA) declines > 30%, > 50%, and > 90%, respectively. Researchers also found that 24 patients had a confirmed radiographic partial response and median overall survival was 24.6 months.
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With respect to safety, 46% of patients had grade 4 neutropenia, 32% had grade 3 anemia, and 11% had grade 3 thrombocytopenia; however, toxicities were manageable and serious infections were rare. Other frequently reported non-hematologic grade 3 adverse events included fatigue (10%) and diarrhea (10%). The most common grade 2 adverse events were anorexia, weight loss, constipation, osteonecrosis of the jaw, rash, and dyspnea.
The authors noted that randomized trials are warranted to confirm the safety and efficacy of this combination antiangiogenic regimen.
- Madan RA, Karzai FH, Ning Y-M, et al. Phase II trial of docetaxel, bevacizumab, lenalidomide, and prednisone in patients with metastatic castration-resistant prostate cancer [published online ahead of print January 18, 2016]. BJU Int. doi: 10.1111/bju.13412.