title: Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.
abstract: BACKGROUND
  Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed.
  
  
  METHODS
  Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided.
  
  
  RESULTS
  Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy.
  
  
  CONCLUSIONS
  Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
authors.affiliation: Division of Medical Oncology, University Hospital, Via Gramsci 14, 43100 Parma, Italy. aardizzoni@ao.pr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.forename: Frank V
authors.initials: FV
authors.lastname: Fossella
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.forename: Davorin
authors.initials: D
authors.lastname: Radosavljevic
authors.forename: Adriano
authors.initials: A
authors.lastname: Paccagnella
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzanti
authors.forename: Donald
authors.initials: D
authors.lastname: Bisset
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin