Phase II Trial of Docetaxel, Bevacizumab, Lenalidomide, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer.

Ravi A Madan, Fatima H Karzai, Yang-Min Ning, Bamidele A Adesunloye, Xuan Huang, Nancy Harold, Anna Couvillon, Guinevere Chun, Lisa Cordes, Tristan Sissung, Shaunna L Beedie, Nancy A Dawson, Marc R Theoret, David G McLeod, Inger Rosner, Jane B Trepel, Min-Jung Lee, Yusuke Tomita, Sunmin Lee, Seth M Steinberg, Philip M Arlen, James L Gulley, William D Figg, William L Dahut,

BJU international, January 18, 2016

To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. Preclinical data have demonstrated the importance of angiogenesis in prostate cancer, but previous clinical trials using angiogenesis inhibitors in combination with docetaxel have not established clinical benefit. The use of multiple anti-angiogenic therapies together may suppress resistance mechanisms and optimize this therapeutic strategy. 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/m2) and prednisone (10mg 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 25mg daily for two weeks followed by one week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary objectives were safety and clinical efficacy. Sixty-three patients enrolled in this trial. Toxicities were manageable with most common adverse events being hematologic ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anemia and 7 (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-hematologic grade 3 adverse events include fatigue (10%) and diarrhea (10%). Grade 2 adverse events in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnea. Of 61 evaluable patients, 57 (93%), 55(90%), and 33(54%) had PSA declines >30%, >50%, and >90% respectively. Twenty-four of 29 patients (86%) had a confirmed radiographic partial response. The median time to progression and overall survival were 18.2 and 24.6 months, respectively. With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. This hypothesis generating data would require randomized trials to confirm these findings. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Pubmed Link: 26780387

DOI: 10.1111/bju.13412