title: Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer: a retrospective study with pharmacogenetic evaluation.
abstract: OBJECTIVE
  In the present study, the combination of carboplatin (CBDCA) plus pemetrexed (PMX) for the treatment of patients with platinum-pretreated, pemetrexed-naïve, advanced non-small cell lung cancer (NSCLC) was investigated. Also, single nucleotide polymorphisms (SNPs) at the XRCC3, XPD, ERCC1, GARFT, DHFR, and TS genes were investigated.
  
  
  METHODS
  Eighty patients treated with CBDCA/PMX at two Italian institutions were evaluable. Of these, 73 patients had blood samples collected for pharmacogenetic evaluation.
  
  
  RESULTS
  Overall, the median age was 59 years (26-78), 59 patients (73.7%) had a performance status of 0, and 34 patients (42.5%) had stage IIIB disease. Thirty-eight patients (47.5%) had responded to prior first-line platinum-based therapy. Study treatment resulted into one complete and 33 partial responses for an overall response rate of 42.5%. The disease control rate was 77.5%. The median progression-free survival (PFS) and overall survival (OS) were 5.8 and 17.4 months, respectively. Responders achieved a significant longer PFS and OS versus non-responders (P = 0.007 and P = 0.003, respectively). The only grade 3-4 adverse event occurring in more than 5.0% of patients was neutropenia (6 patients, 7.5%). No statistically significant association was noted between polymorphisms of the genes analyzed and clinical outcome.
  
  
  CONCLUSIONS
  In patients with platinum-pretreated, advanced NSCLC and favorable clinical prognostic factors, treatment with CBDCA/PMX is associated with a good clinical outcome and toxicity profile. None of the SNPs analyzed was found to be a useful predictor of treatment efficacy.
authors.affiliation: Division of Medical Oncology, Azienda Ospedaliera Santa Maria della Misericordia, Via Dottori 1, 06156 Perugia, Italy. giulio.metro@yahoo.com
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.forename: R
authors.initials: R
authors.lastname: Chiari
authors.forename: M
authors.initials: M
authors.lastname: Mare
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: F R
authors.initials: FR
authors.lastname: Tofanetti
authors.forename: V
authors.initials: V
authors.lastname: Minotti
authors.forename: M
authors.initials: M
authors.lastname: Ferraldeschi
authors.forename: D
authors.initials: D
authors.lastname: Giuffrida
authors.forename: L
authors.initials: L
authors.lastname: Marcomigni
authors.forename: C
authors.initials: C
authors.lastname: Bennati
authors.forename: M J
authors.initials: MJ
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Meacci
authors.forename: R
authors.initials: R
authors.lastname: Bellavita
authors.forename: L
authors.initials: L
authors.lastname: Pistola
authors.forename: V
authors.initials: V
authors.lastname: Ludovini
authors.forename: L
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D004268:DNA-Binding Proteins; D005971:Glutamates; C110901:X-ray repair cross complementing protein 3; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases