title: Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.
abstract: OBJECTIVE
  The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer.
  
  
  METHODS
  Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy.
  
  
  RESULTS
  A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months).
  
  
  CONCLUSIONS
  The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.
authors.affiliation: *Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. kayamada@med.kurume-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeoka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Zaizen
authors.forename: Fumie
authors.initials: F
authors.lastname: Yamashita
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Naito
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okayama
authors.forename: Maki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D048550:Hepatic Insufficiency / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin
keywords: carboplatin; elderly; non-small cell lung cancer; pemetrexed