title: Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  At least three or four patients were entered at each dose level. The starting dose was 20 mg/m(2) for VRB on days 1 and 8 and 4 mg/m(2) for MMC on day 1, with a fixed dose of P 80 mg/m(2) on day 1 every 4 weeks. MMC was increased to 6 mg/m(2) at dose level 2 and subsequently to 8 mg/m(2) at dose level 4. At dose level 3, VRB was increased to 25 mg/m(2). Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study.
  
  
  RESULTS
  Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m(2) on days 1 and 8 and MMC 8 mg/m(2) and P 80 mg/m(2) on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in </= 25% of patients over two courses. Of the 25 assessable patients in the phase I study, 13 achieved a partial response and one had a complete response for a response rate of 56. 0%. Of the 19 assessable patients in the phase II study, 12 had a partial response (63.2%; 95% confidence interval, 38.4% to 83.7%). Grade 3 and 4 leukopenia was observed in 19 (100%), and grade 3 thrombocytopenia was seen in seven (36.8%). Median survival time was 10.7 months and the 1-year survival rate was 43.2% in the 44 assessable patients.
  
  
  CONCLUSIONS
  The VRB/MMC/P regimen is effective against NSCLC, and its efficacy should be confirmed through a randomized study.
authors.affiliation: Department of Internal Medicine, National Kinki Central Hospital for Chest Diseases, Sakai, Osaka, Japan. ha7k-frs@asahi-net.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Furuse
authors.forename: M
authors.initials: M
authors.lastname: Kawahara
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
authors.forename: M
authors.initials: M
authors.lastname: Takada
authors.forename: M
authors.initials: M
authors.lastname: Miyashita
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D016685:Mitomycin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine