title: Phase I study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  This trial was conducted to determine the maximum tolerated dose (MTD), principal toxicity, and recommended dose for phase II study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with previously untreated NSCLC, either stage IIIB with pleural effusion or stage IV, were eligible if they had a performance status of 0-2, were 75 years or younger, and had adequate organ function. The respective doses of nedaplatin (day 1) and weekly paclitaxel (days 1, 8, and 15) studied were 80/60, 80/70, 80/80, 80/90, and 100/90 (mg m(-2)), repeated every 4 weeks.
  
  
  RESULTS
  From May 2004 through June 2005, 21 patients (18 men and 3 women; median age, 63 years; age range, 53-75 years) were enrolled. The MTD was determined to be 100 mg m(-2) of nedaplatin and 90 mg m(-2) of weekly paclitaxel. Dose-limiting toxicities at the MTD were neutropenic fever and hepatic dysfunction. We recommend doses of 80 mg m(-2) of nedaplatin and 90 mg m(-2) of weekly paclitaxel for phase II study. Grade 3-4 hematologic toxicities included neutropenia in 29% of patients, thrombocytopenia in 0%, and anemia in 5%. Although the most frequent non-hematologic toxicity was hepatic dysfunction, all cases were only mildly to moderately severe. Although two patients had grade 3 or 4 pulmonary toxicity due to Pneumocystis carinii pneumonia, these patients recovered after receiving trimetoprim-sulfamethoxazole, steroid therapy, and supplemental oxygen. There were no treatment-related deaths. The overall response rate was 19.0% (95% confidence interval, 5.4-41.9%), and all responses were in patients receiving the recommended doses. The median dose-intensities for nedaplatin and paclitaxel were 91.6 and 87.1%, respectively, of the planned doses.
  
  
  CONCLUSIONS
  This combination chemotherapy is active and well tolerated and warrants phase II study.
authors.affiliation: The First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8666, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirose
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ishida
authors.forename: Sojiro
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Tomohide
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kohichi
authors.initials: K
authors.lastname: Ando
authors.forename: Takao
authors.initials: T
authors.lastname: Shirai
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Naoya
authors.initials: N
authors.lastname: Horichi
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohmori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; C053989:nedaplatin; D017239:Paclitaxel