title: Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer.
abstract: BACKGROUND
  To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer.
  
  
  METHODS
  Patients received paclitaxel doses of 150-210 mg/m2 given over 3 h and cisplatin doses of 60-80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion.
  
  
  RESULTS
  A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hematological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m2, which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug-drug interaction between the 3 h infusion paclitaxel and cisplatin.
  
  
  CONCLUSIONS
  The recommended doses for further study are determined to be paclitaxel 180 mg/m2 and cisplatin 80 mg/m2. This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.
authors.affiliation: Thoracic Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kurata
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Shinkai
authors.forename: Y
authors.initials: Y
authors.lastname: Ohe
authors.forename: H
authors.initials: H
authors.lastname: Kunitoh
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: R
authors.initials: R
authors.lastname: Kakinuma
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Omatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: N
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D017239:Paclitaxel; D002945:Cisplatin