Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration‐resistant prostate cancer. (19th February 2016)

• Record Type: Journal Article
• Authors: Madan, Ravi A.; Karzai, Fatima H.; Ning, Yang‐Min; Adesunloye, Bamidele A.; Huang, Xuan; Harold, Nancy; Couvillon, Anna; Chun, Guinevere; Cordes, Lisa; Sissung, Tristan; Beedie, Shaunna L.; Dawson, Nancy A.; Theoret, Marc R.; McLeod, David G.; Rosner, Inger; Trepel, Jane B.; Lee, Min‐Jung; Tomita, Yusuke; Lee, Sunmin; Chen, Clara; Steinberg, Seth M.; Arlen, Philip M.; Gulley, James L.; Figg, William D.; Dahut, William L.
• Is Part Of: BJU international. Volume 118:Number 4(2016:Aug.)
• Page Start: 590
• Page End: 597
• Publication Date: 2016-02-19
• Subjects: prostate cancer -- angiogenesis inhibition -- combinationation therapy -- metastatic castration resistant prostate cancer -- docetaxel coimbination; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.13412
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract : Objective: To determine the safety and clinical efficacy of two anti‐angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. Patients and methods: Eligible patients with metastatic castration‐resistant prostate cancer enrolled in this open‐label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m 2 ) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3‐week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy. Results: A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty‐nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non‐haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively. Conclusions: With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis‐generating data would require randomized trials to confirm the findings.