title: Phase I/II study of cisplatin, ifosfamide and irinotecan with rhG-CSF support in patients with stage IIIB and IV non-small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I/II study in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) to: (1) determine the maximum tolerated dose (MTD) of cisplatin combined with a fixed schedule of ifosfamide and irinotecan with rhG-CSF support; and (2) to determine the overall response rate and median survival of patients entered on this study.
  
  
  METHODS
  Ifosfamide (1.5 g/m2) and irinotecan (60 mg/m2) were administered at fixed doses on days 1-4 and on days 1, 8 and 15, respectively. Cisplatin was given on day 1 at 60 mg/m2 and was increased in 10-mg/m2 increments. This regimen was repeated every 4 weeks. rhG-CSF (nartograstim) was administered subcutaneously at a dose of 1 microg/kg on days 5-18 except on the day of irinotecan treatment.
  
  
  RESULTS
  Between June 1995 and April 1998, 46 patients were registered onto this phase I/II study. The MTD of cisplatin was defined according to toxicity and the dose during three courses was increased. Since at the 80 mg/m2 dose level more than one-third of the patients were treated with dose modification, the dose of 70 mg/m2 was recommended for phase II study. The dose-limiting toxicity was leukopenia. The overall response rate was 62.2% (95% CI 48.0-76.4%, the median response duration was 144 days, and the median survival time was 393 days.
  
  
  CONCLUSIONS
  For phase II study, we recommend doses of cisplatin 70 mg/m2 on day 1 combined with ifosfamide and irinotecan with rhG-CSF support. Both the response rate and preliminary survival data in this study suggest a high degree of activity of this combination in previously untreated NSCLC.
authors.affiliation: Division of Respiratory Disease, Minami-ichijo Hospital, Sapporo, Japan. afujita@sa2.so-net.ne.jp
authors.forename: A
authors.initials: A
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Takabatake
authors.forename: S
authors.initials: S
authors.lastname: Tagaki
authors.forename: K
authors.initials: K
authors.lastname: Sekine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; 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* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000077146:Irinotecan; D002945:Cisplatin; D007069:Ifosfamide; D002166:Camptothecin