title: Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer.
abstract: OBJECTIVE
  CPT-11 (60 mg/m2 on days 1, 8 and 15) in combination with CDDP (80 mg/m2 on day 1) has shown promising antitumor activity for non-small-cell lung cancer (NSCLC), but dose-limiting toxicities (DLT) are leukopenia and diarrhea, with a wide variation among patients. To estimate weekly CDDP administration in combination with CPT-11, a phase I study for patients with advanced NSCLC was conducted.
  
  
  METHODS
  Patients were treated with CPT-11 at a fixed dose of 60 mg/m2 together with CDDP at 27 mg/m2 (level 1, 6 patients), 33 mg/m2 (level 2, 12 patients), and 40 mg/m2 (level 3, 6 patients) with 1600 ml hydration on days 1, 8 and 15 over 4 weeks. During the treatment course, drug was not administered on the day it was due in the presence of leukopenia (< 3000/ml) and/or diarrhea.
  
  
  RESULTS
  The planned administration was completed in 5 of 6 patients at level 1, 6 of 12 patients at level 2, and 2 of 6 patients at level 3. The most common toxicity observed was leukopenia (five patients with grade 3 and one patient with grade 4). Leukopenia was considered to be a DLT, and the maximum tolerated dose (MTD) was level 2. Although there were patients who suffered from diarrhea (four patients with higher than grade 2), diarrhea was judged not to be a DLT with this weekly regimen. Nausea and vomiting were mild. Pharmacokinetic analysis of free platinum from CDDP demonstrated that the area under the curve (AUC) from 33 mg/m2 CDDP was 0.92 +/- 0.29 microg/ml h. In 13 patients evaluated for response, the response rate was 54%.
  
  
  CONCLUSIONS
  The value of weekly administration of CDDP in combination with CPT-11 was shown by (1) diarrhea not being dose-limiting, (2) mild nausea, (3) well-maintained AUC of free platinum, and (4) promising activity.
authors.affiliation: Department of Respiratory Medicine, International Medical Center of Japan, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Shinbara
authors.forename: M
authors.initials: M
authors.lastname: Kamimura
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Kudo
authors.forename: J
authors.initials: J
authors.lastname: Kabe
authors.forename: S
authors.initials: S
authors.lastname: Hibino
authors.forename: M
authors.initials: M
authors.lastname: Hino
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003967:Diarrhea; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin