Results from a phase II investigator initiated study of lenalidomide (Revlimid?, Celgene) in combination with bevacizumab (Avastin?, Genentech/Roche), docetaxel (Taxotere?, Sanofi-Aventis) and prednisone in patients with metastatic castration-resistant prostate cancer were presented at the 47th annual meeting of the American Society of Clinical Oncology in Chicago, Ill.
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.
Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom-free, and since men with the condition are older they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. About 2/3 of cases are slow growing, the other third more aggressive and fast developing.
In the study, patients with chemotherapy na?ve, progressive mCRPC were treated with docetaxel (75 mg/m2) and bevacizumab (15 mg/kg) on day one, plus lenalidomide (25 mg) on days 1-14, with daily prednisone (10 mg) and enoxaparin (Lovenox, Sanofi-Aventis) during each 21-day cycle.
At the time of presentation, 46 of the planned 51 patients were enrolled. The overall PSA response rate was 86.4% (38/44). More than 70% (31/44) of the patients on the trial had a reduction in PSA of at least 75%. Of 24 patients with measurable disease, the overall RECIST response rate was 87.5%, with one complete response, 20 partial responses and 3 patients with stable disease. >BR>
Grade 3 or higher toxicities in the study included neutropenia (39% 18/46), anemia (13% 6/46), infection (13% 6/46) and thrombocytopenia (9% 4/46). One patient had hypertension and two had febrile neutropenia. Two patients had perianal fistula. Osteonecrosis of the jaw occurred in 30% (14/46). Of these patients, nine had concomitant and four had a history of bisphosphonate use.
Lenalidomide is approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. The drug is an IMiDs? compound and continues to be evaluated in over 300 clinical trials.
The combination of lenalidomide and docetaxel/prednisone for the initial treatment of patients with metastatic castration resistant prostate cancer is currently being evaluated in a pivotal Phase III trial.
 A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination With Docetaxel and Prednisone for Patients With Castrate-Resistant Prostate Cancer (Mainsail)