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, Clara ChenSeth M. Steinberg, Philip M. Arlen, James L. Gulley, William D. Figg*, William L. Dahut

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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/m2) 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.

Original languageEnglish
Pages (from-to)590-597
Number of pages8
JournalBJU International
Volume118
Issue number4
DOIs
StatePublished - 1 Oct 2016
Externally publishedYes

Keywords

  • angiogenesis inhibition
  • combinationation therapy
  • docetaxel coimbination
  • metastatic castration resistant prostate cancer
  • prostate cancer

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