title: The safety and efficacy of gefitinib versus platinum-based doublets chemotherapy as the first-line treatment for advanced non-small-cell lung cancer patients in East Asia: a meta-analysis.
abstract: BACKGROUND
  To evaluate the risk/benefit profiles of gefitinib in comparison with platinum-based doublets chemotherapy as a first-line treatment for chemonaïve patients with advanced non-small-cell lung cancer in East Asia.
  
  
  METHODS
  We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov to identify randomized and non-randomized phase II or III clinical trials of gefitinib or chemotherapy treatment in East Asian patients published before 4/30/2007. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Treatment arms with gefitinib 250mg/day and platinum-based doublets chemotherapy irrespective of dosage and schedule were combined to calculate the pooled estimates for efficacy and safety outcomes of interest.
  
  
  RESULTS
  We identified 7 gefitinib and 41 platinum-based doublets chemotherapy trials with nearly 3000 enrolled patients for planned comparison. The pooled response rate (95% confidence interval) to gefitinib for unselected chemonaïve population was 31% (23-38%), not substantially different from 34% (31-38%) reported by platinum-based doublets chemotherapy trials. Patients with certain characteristics were more likely to benefit from gefitinib treatment, with pooled response rates as high as 75% (60-90%) for patients with epidermal growth factor receptor (EGFR) exon 18-21 mutations; 56% (38-74%) for never smokers; 55% (41-69%) for female; and 43% (30-57%) for adenocarcinoma or bronchioalveolar carcinoma. Severe hematological adverse events related to gefitinib treatment were not observed in any of the included trials. However, the risks of severe liver and lung injury related to gefitinib treatment were both approximately 6%, significantly higher than 1% and 0.2% reported by platinum-based doublets chemotherapy trials.
  
  
  CONCLUSIONS
  Our data suggest that one third of chemonaïve NSCLC patients in East Asia would respond to oral gefitinib monotherapy while 6% would develop severe liver and lung injury. Although patients with EGFR gene mutations, female gender, non-smokers, or adenocarcinoma were more likely to respond to gefitinib, further study with valid comparison groups are needed to identify the optimal treatment strategy in these subpopulations.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Yinong
authors.initials: Y
authors.lastname: Young-Xu
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
authors.forename: E John
authors.initials: EJ
authors.lastname: Orav
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005202:Asia, Eastern; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D017671:Platinum Compounds / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D011799:Quinazolines; D000077156:Gefitinib