title: Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone.
  
  
  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.
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Fatima H
authors.initials: FH
authors.lastname: Karzai
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Ning
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Bamidele A
authors.initials: BA
authors.lastname: Adesunloye
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Harold
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Couvillon
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Guinevere
authors.initials: G
authors.lastname: Chun
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cordes
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Tristan
authors.initials: T
authors.lastname: Sissung
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Shaunna L
authors.initials: SL
authors.lastname: Beedie
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Dawson
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Theoret
authors.affiliation: Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
authors.affiliation: Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Inger
authors.initials: I
authors.lastname: Rosner
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Trepel
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Sunmin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Radiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Clara
authors.initials: C
authors.lastname: Chen
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. wdfigg@helix.nih.gov.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D000068258:Bevacizumab; D013792:Thalidomide; D000077269:Lenalidomide; D011241:Prednisone
keywords: angiogenesis inhibition; combinationation therapy; docetaxel coimbination; metastatic castration resistant prostate cancer; prostate cancer