title: Phase I clinical trial of lenalidomide in combination with bevacizumab in patients with advanced cancer.
abstract: Lenalidomide and bevacizumab have antitumor activity in various tumor types. We conducted a phase I study of this combination in patients with advanced cancer.
  
  
  
  A "3 + 3" study design was used. Lenalidomide 10 or 20 mg (orally, days 1-21) and bevacizumab 5, 7.5, or 10 mg/kg, (intravenously, every 2 weeks) were given at four escalating dose levels, followed by an expansion phase at the highest maximum tolerated dose (MTD) (1 cycle = 4 weeks). Dose-limiting toxicity (DLT), MTD, adverse events, and clinical outcomes were assessed.
  
  
  
  Thirty-one patients were enrolled (median age, 60 years; men, 52 %). The most common tumor types were colorectal carcinoma (n = 11) and melanoma (n = 5). Overall, 105 cycles (median, 2) were administered. No DLTs were observed. The maximum tested dose (level 4) was used in the expansion phase. The most common toxicities were fatigue (n = 7, 23 %) and skin rash (n = 4, 13 %). One patient developed a transient ischemic attack (3.2 %); prophylactic anticoagulation became mandatory in the subsequent 17 treated patients. Of 31 patients, 27 were evaluable for response. Stable disease (SD) was noted in 10 (37 %) patients, including five patients with SD for ≥6 months (tumor types: clear cell sarcoma, germ cell tumor, colorectal carcinoma, and melanoma). The median progression-free survival and overall survival were 2.8 and 5.5 months, respectively.
  
  
  
  The combination of lenalidomide with bevacizumab in patients with advanced solid tumors was safe. Prolonged stable disease was noted in selected tumor types, warranting further clinical evaluation.
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.|Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Rabih
authors.initials: R
authors.lastname: Said
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kakadiaris
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.affiliation: Sarah Research Institute at HealthOne, Denver, CO, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Falchook
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Novartis, Cambridge, MA, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, PA, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Zinner
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Moores Cancer Center, San Diego, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. atsimber@mdanderson.org.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D066066:Response Evaluation Criteria in Solid Tumors; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000068258:Bevacizumab; D013792:Thalidomide; D000077269:Lenalidomide
keywords: Advanced cancer; Bevacizumab; Lenalidomide; Phase I trial