title: Dose escalation and pharmacokinetic study of carboplatin plus pemetrexed for elderly patients with advanced nonsquamous non-small-cell lung cancer: Kumamoto thoracic oncology study group trial 1002.
abstract: OBJECTIVE
  This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed.
  
  
  METHODS
  The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance.
  
  
  CONCLUSIONS
  For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities.
authors.affiliation: Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakata
authors.forename: Jiichiro
authors.initials: J
authors.lastname: Sasaki
authors.forename: Sho
authors.initials: S
authors.lastname: Saeki
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kishi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Notsute
authors.forename: Ryo
authors.initials: R
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Saruwatari
authors.forename: Toyohisa
authors.initials: T
authors.lastname: Iriki
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Akaike
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujii
authors.forename: Susumu
authors.initials: S
authors.lastname: Hirosako
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; 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* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D014018:Tissue Distribution
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin