title: Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer: JCOG 9910-DI.
abstract: OBJECTIVE
  Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC.
  
  
  METHODS
  Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m(2) and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/2), five at level 4 (80/2) and three at level 5 (90/2).
  
  
  RESULTS
  One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C(max)) and the duration of plasma concentration >50 ng/ml of paclitaxel.
  
  
  CONCLUSIONS
  Weekly combined paclitaxel (up to 90 mg/m(2)) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.
authors.affiliation: Yokohama Municipal Citizen's Hospital, Yokohama, Japan. knaoki@pg7.so-net.ne.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunikane
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fujii
authors.forename: Shuko
authors.initials: S
authors.lastname: Tsujimura
authors.forename: Naoya
authors.initials: N
authors.lastname: Hida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Koshiro
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel