title: Phase I study of second-line chemotherapy with docetaxel and carboplatin in advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Docetaxel and carboplatin have a broad spectrum of antitumor activity. We conducted a phase I study of docetaxel and carboplatin as second-line chemotherapy in previously treated non-small-cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this second-line combination chemotherapy.
  
  
  METHODS
  Patients with advanced NSCLC were treated with escalating docetaxel doses in combination with a fixed-target area under the concentration-time curve (AUC) of 5 mg min/ml of carboplatin on day 1 of a 3-4-week cycle. The carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The docetaxel dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2 increments.
  
  
  RESULTS
  A total of 16 patients previously treated with anticancer drugs were enrolled through three dose levels (40, 50 and 60 mg/m2 of docetaxel). All patients were assessable for toxicity and response. The MTD was docetaxel 60 mg/m2 with a carboplatin target AUC of 5 mg min/ml, and the dose-limiting toxicities in two of four patients were neutropenia and thrombocytopenia. Overall, neutropenia and thrombocytopenia of grade 3/4 occurred in eight patients (50%) and three patients (19%), respectively. Four patients (25%) and two patients (13%) experienced both grade 1 diarrhea and dermatitis, respectively. Allergic reactions, fluid retention, pneumonitis, neurotoxicity and mucositis were not observed. Of 16 patients, 5 showed an objective response (response rate 31%; 95% CI 14-56%).
  
  
  CONCLUSIONS
  The combination of docetaxel and carboplatin is a feasible and well-tolerated second-line chemotherapy regimen in the treatment of NSCLC. Docetaxel 50 mg/m2 under the carboplatin target AUC of 5 mg x min/ml using the Chatelut formula was the recommended dose for phase II study.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan. okamikio@net.nagasaki-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: S
authors.initials: S
authors.lastname: Nagashima
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: H
authors.initials: H
authors.lastname: Soda
authors.forename: S
authors.initials: S
authors.lastname: Doi
authors.forename: F
authors.initials: F
authors.lastname: Narasaki
authors.forename: M
authors.initials: M
authors.lastname: Suenaga
authors.forename: H
authors.initials: H
authors.lastname: Takatani
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: J
authors.initials: J
authors.lastname: Tsurutani
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003872:Dermatitis / Q000209:etiology; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D043823:Taxoids; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel