title: Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group.
abstract: OBJECTIVE
  This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naive patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m(2) for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progression-free survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS).
  
  
  RESULTS
  Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile.
  
  
  CONCLUSIONS
  Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, East KS-159, Boston, MA, USA. dmcdermo@bidmc.harvard.edu
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Linette
authors.forename: Jon
authors.initials: J
authors.lastname: Richards
authors.forename: James W
authors.initials: JW
authors.lastname: Jakub
authors.forename: Muralidhar
authors.initials: M
authors.lastname: Beeram
authors.forename: Stefano
authors.initials: S
authors.lastname: Tarantolo
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Agarwala
authors.forename: Gary
authors.initials: G
authors.lastname: Frenette
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Lee
authors.initials: L
authors.lastname: Cranmer
authors.forename: Karl
authors.initials: K
authors.lastname: Lewis
authors.forename: John
authors.initials: J
authors.lastname: Kirkwood
authors.forename: J Michael
authors.initials: JM
authors.lastname: White
authors.forename: Chenghua
authors.initials: C
authors.lastname: Xia
authors.forename: Kiran
authors.initials: K
authors.lastname: Patel
authors.forename: Evan
authors.initials: E
authors.lastname: Hersh
mesh_terms: D000284:Administration, Oral; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib