title: Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902.
abstract: OBJECTIVE
  This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed.
  
  
  METHODS
  Forty-one patients received CBDCA at a dose targeting an area under the concentration-time curve of 5 mg/mL × min and PEM of 500 mg/m(2) on day 1 every 3 weeks. Single-nucleotide polymorphisms of the thymidylate synthase (TYMS) coding gene, the variable number of tandem repeat (VNTR) in the TYMS, and the methylenetetrahydrofolate reductase (MTHFR) coding gene were analyzed.
  
  
  RESULTS
  The overall RR was 36.6 %. Median progression-free survival and median survival time were 4.7 months [95 % confidence interval (CI) 3.9-5.6 months] and 16.2 months (95 % CI 6.1-26.2 months), respectively. Epidermal growth factor receptor gene mutations were detected in 6 patients (14.6 %). The VNTR in the TYMS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038).
  
  
  CONCLUSIONS
  This combination therapy was effective and tolerable in patients with advanced non-sq NSCLC. The VNTR in the TYMS appears to be a predictive factor for anemia and thrombocytopenia in patients treated with this regimen.
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan, k-kenya@fmu.ac.jp.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kanazawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujita
authors.forename: Satoru
authors.initials: S
authors.lastname: Fujiuchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.forename: Kei
authors.initials: K
authors.lastname: Takamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Katsuura
authors.forename: Osamu
authors.initials: O
authors.lastname: Honjo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kojima
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; D013940:Thymidylate Synthase; D066246:ErbB Receptors