title: Treatments for metastatic melanoma: synthesis of evidence from randomized trials.
abstract: BACKGROUND
  Advanced melanomas (non-resectable Stage-III/IV) are fatal, with few effective treatments. It remains unclear if other drugs offer improvements over the standard, dacarbazine.
  
  
  OBJECTIVE
  We quantified objective response rates (Complete+Partial response) of dacarbazine versus comparators for advanced cutaneous melanoma.
  
  
  METHODS
  We retrieved all head-to-head randomized controlled trials involving dacarbazine and other drugs/combinations. Two reviewers searched MEDLINE (1966-Jan 2006), EMBASE (1980-2006), CINAHL (1982-2006) and Cochrane library, then compared results. Differences were resolved through consensus. Rates were combined using random effects meta-analysis. chi2 tested heterogeneity; points from Jadad's method were assessed to examine study quality.
  
  
  RESULTS
  We found 48 studies having 111 active treatment arms [24 with dacarbazine monotherapy (n=1390), 75 with dacarbazine combinations (n=4962), and 12 with non-dacarbazine treatments (n=783)] treating 7135 patients. Overall, study quality was poor. Response to dacarbazine monotherapy ranged between 5.3% and 28.0% (average 15.3%), OR=1.31, CI(95%): 1.06-1.61; N=3356. Partial responses comprised 73% of successes. Only adding interferons improved response rates (OR=1.69, CI(95%): 1.07-2.68, N=778) but survival duration was not significantly longer (P=0.32), and trials with larger sample sizes found lower success rates. All other treatments alone or in combination were ineffective P>0.05.
  
  
  CONCLUSIONS
  Dacarbazine generally produces poor outcomes. Adding other therapies offers minimal clinical advantages (possibly with interferons). In general, study quality was poor and sample sizes were small. This meta-analysis highlights the unmet need for effective treatment options for advanced melanoma.
authors.affiliation: Leslie Dan Faculty of Pharmacy, 144 College Street, Toronto, ON, Canada M5S 3M2. philip.lui@utoronto.ca
authors.forename: Philip
authors.initials: P
authors.lastname: Lui
authors.forename: Richard
authors.initials: R
authors.lastname: Cashin
authors.forename: Márcio
authors.initials: M
authors.lastname: Machado
authors.forename: Michiel
authors.initials: M
authors.lastname: Hemels
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Corey-Lisle
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Einarson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D003606:Dacarbazine / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine