Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer.

Autor: Madan RA; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Karzai FH; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Ning YM; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Adesunloye BA; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Huang X; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Harold N; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Couvillon A; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Chun G; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Cordes L; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Sissung T; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Beedie SL; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Dawson NA; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA., Theoret MR; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., McLeod DG; Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA., Rosner I; Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA., Trepel JB; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Lee MJ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Tomita Y; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Lee S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Chen C; Radiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Steinberg SM; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Arlen PM; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Gulley JL; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Figg WD; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. wdfigg@helix.nih.gov., Dahut WL; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: BJU international [BJU Int] 2016 Oct; Vol. 118 (4), pp. 590-7. Date of Electronic Publication: 2016 Feb 19.
DOI: 10.1111/bju.13412
Abstrakt: 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.
(Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)
Databáze: MEDLINE
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