title: Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer.
abstract: BACKGROUND
  Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells in a xenograft model. We conducted a Phase I study of lenalidomide and sorafenib in patients with advanced cancer.
  
  
  METHODS
  During the escalation phase, lenalidomide (days 1-21) and sorafenib (days 1-28) were given orally once daily at the following respective doses: level 1 (10 mg, 200 mg); level 2 (10 mg, 400 mg); level 3 (20 mg, 400 mg); and level 4 (25 mg, 400 mg) (1 cycle = 28 days). A "3 + 3" study design was used.
  
  
  RESULTS
  Forty-one patients were treated (median age: 50 years). The most common diagnoses were adenoid cystic carcinoma (N = 9), ovarian adenocarcinoma (N = 7), and melanoma (N = 6); 142 cycles (median: 3) were administered. No dose-limiting toxicities were noted. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3-4 treatment-related toxicities were neutropenia, thrombocytopenia, skin rash, and thromboembolism. Of 38 patients who were evaluable for response, stable disease (SD) was noted in 53 % of patients (SD ≥6 months: 16 %). Tumor types with SD ≥ 6 months were as follows: ocular melanoma, 2/2 (100 %); other melanoma, 1/4 (25 %); adenoid cystic carcinoma, 2/9 (22 %); and ovarian cancer, 1/6 (17 %). The median progression-free survival duration was 3.5 months (95 % CI, 1.9-5.0), and the median overall survival duration was 12.3 months (95 % CI, 10.1-14.5).
  
  
  CONCLUSIONS
  Lenalidomide and sorafenib was well tolerated and associated with disease stabilization for ≥6 months in patients with melanoma, adenoid cystic carcinoma, and ovarian adenocarcinoma.
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: Prasanth
authors.initials: P
authors.lastname: Ganesan
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Gerald
authors.initials: G
authors.lastname: Falchook
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wheler
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Shell
authors.initials: S
authors.lastname: Laday
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Merrill
authors.initials: M
authors.lastname: Kies
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000077157:Sorafenib; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult; D048490:raf Kinases / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D007155:Immunologic Factors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D013792:Thalidomide; D000077157:Sorafenib; D048490:raf Kinases; D000077269:Lenalidomide