title: Results of a multicenter, randomized, double-blind, dose-evaluating phase 2/3 study of lenalidomide in the treatment of metastatic malignant melanoma.
abstract: BACKGROUND
  There are currently no systemic treatments for stage IV melanoma, which have been proven in randomized trials to benefit overall survival (OS). Lenalidomide has efficacy against melanoma in animal models and safety in phase 1 trials. The authors reported the results of a phase 2/3 study comparing the safety and efficacy of 2 doses of lenalidomide in patients with relapsed metastatic melanoma disease refractory to previous treatment with dacarbazine, temozolomide, interleukin-2, or interferon-alpha.
  
  
  METHODS
  A total of 294 patients were randomized to oral lenalidomide at 5 mg or 25 mg dose. Tumor response, time to progression, and OS were evaluated. Treatment continued until disease progression or unacceptable adverse events.
  
  
  RESULTS
  No significant differences in response rate, OS, or time to progression were observed between lenalidomide 25 mg versus 5 mg (overall response rate: 5.5% vs 3.4%, P = .38; median OS: 6.8 months vs 7.2 months, P = .71; and median time to progression: 2.2 months vs 1.9 months, P = .24). Myelosuppression was observed in 37.0% of patients in the 25 mg group and 13.7% of patients in the 5 mg group. Treatment-related serious adverse events were seen in 39.0% of patients at the 25 mg dose and 35.4% of patients at the 5 mg dose.
  
  
  CONCLUSIONS
  Despite the occurrence of treatment-related serious adverse events, approximately 80% of patients continued treatment. The higher dose of lenalidomide did not improve response rate, time to progression, or OS of patients with relapsed/refractory stage IV melanoma. A parallel placebo-controlled study has been conducted to further assess the efficacy of lenalidomide in stage IV melanoma patients.
authors.affiliation: Department of Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA. jglaspy@mednet.ucla.edu
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Jon M
authors.initials: JM
authors.lastname: Richards
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Agarwala
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Robert D
authors.initials: RD
authors.lastname: Knight
authors.forename: J Ulf
authors.initials: JU
authors.lastname: Jungnelius
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019233:Retreatment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide