title: Phase I and pharmacologic study of docetaxel and irinotecan in advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The starting doses of docetaxel/CPT-11 were 30/40 mg/m(2), and doses were escalated in 10-mg/m(2) increments until the MTD was reached.
  
  
  RESULTS
  The MTD of docetaxel/CPT-11 was 50/60 mg/m(2) (level 5A), or 60/50 mg/m(2) (level 5B). Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30 patients. The median survival time was 48 weeks, and the 1-year survival rate was 44.9%.
  
  
  CONCLUSIONS
  The combination of docetaxel and CPT-11 seems to be active against NSCLC, with acceptable toxicity. The recommended dose for phase II studies is 50 mg/m(2) of CPT-11 (days 1, 8, and 15) and 50 mg/m(2) of docetaxel (day 2) administered every 28 days.
authors.affiliation: Departments of Internal Medicine, Osaka Prefectural Habikino Hospital and Kinki University School of Medicine, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.forename: S
authors.initials: S
authors.lastname: Negoro
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Saka
authors.forename: M
authors.initials: M
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Niitani
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008870:Microtubules / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin