title: CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11, a new derivative of camptothecin, in combination with a fixed dose of cisplatin in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Twenty-seven previously untreated patients with stage IIIB or IV NSCLC were assessable for toxicity, and 26 were assessable for response. The initial dose of CPT-11 was 30 mg/m2 given as a 90-minute intravenous (IV) infusion on days 1, 8, and 15 in combination with cisplatin (80 mg/m2 IV on day 1) given every 4 weeks. The dose of CPT-11 was escalated in increments of 10 mg/m2 until severe or life-threatening toxic effects were observed.
  
  
  RESULTS
  Significant toxicity was infrequent up to 60 mg/m2 of CPT-11. The maximum-tolerated toxicity was reached at a dose of 70 mg/m2. Three of six patients either had leukocyte count nadirs of less than 2,000/microL or experienced grade 4 diarrhea during the first cycle of therapy at 70 mg/m2. The major toxic effects were leukopenia and diarrhea. There were 14 partial responses (54%) among the 26 patients.
  
  
  CONCLUSIONS
  A combination of CPT-11 and cisplatin seems to be effective against NSCLC with acceptable toxicities. The recommended dose for phase II studies is 60 mg/m2 of CPT-11 on days 1, 8, and 15, and 80 mg/m2 of cisplatin on day 1 every 4 weeks.
authors.affiliation: Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
authors.forename: M
authors.initials: M
authors.lastname: Takada
authors.forename: Y
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: S
authors.initials: S
authors.lastname: Negoro
authors.forename: K
authors.initials: K
authors.lastname: Matsui
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: N
authors.initials: N
authors.lastname: Takifuji
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: S
authors.initials: S
authors.lastname: Kishimoto
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin