title: Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced non-small-cell lung cancer.
abstract: BACKGROUND
  The aim of this study was to evaluate feasibility and tolerability of the three-drug combination of paclitaxel, ifosfamide and carboplatin (TIC) in patients with advanced non-small-cell lung cancer. The specific objectives of the study were: (i) to define the dose-limiting toxicities (DLTs) and the maximum-tolerated dose of ifosfamide administered as part of the combination; and (ii) to determine the overall response rate and overall survival of patients treated with this regimen.
  
  
  METHODS
  Patients with untreated, stage IIIB (pleural effusion) or stage IV non-small-cell lung cancer were enrolled in one of three cohorts. Patients received paclitaxel 200 mg/m(2) as a 1-h infusion on day 1 with carboplatin at an area under the concentration-time curve (AUC) of 6 mg.min/ml on day 2. For dose level I, ifosfamide was administered at a dose of 2 g/m(2) on days 1 and 2. For dose levels II and III, the dose of ifosfamide was decreased to 1.5 g/m(2) on days 1 and 2 and the dose of carboplatin was decreased to AUC 5 mg.ml/min. Therapy for dose levels I and III included filgrastim support (5 micro g/kg/day), which was initiated on day 3 and continued until after day 11 or until an absolute neutrophil count >10 000/ micro l. Treatment cycles were repeated every 21 days. Once the phase II dose was established, a full cohort of patients received therapy at this dose level to examine further the regimen's activity and tolerability.
  
  
  RESULTS
  Neutropenia was the DLT encountered for dose levels I and II. No DLT was encountered in the initial six patients treated at dose level III, and therefore this dose level was declared the recommended phase II dose. A total of 49 patients were treated at the recommended phase II dose. The predominant non-hematological toxicity encountered with this triplet regimen was cumulative peripheral neuropathy. Of the 65 eligible patients enrolled in this study, 17 (26%) responded. There were 15 patients with partial responses (23%), two with regression, and 26 with stabilization of disease (40%). Median progression-free and overall survival were 4.8 and 9.4 months, respectively.
  
  
  CONCLUSIONS
  The combination TIC is well-tolerated. This triplet regimen produced response and survival rates in advanced non-small-cell lung cancer similar to those of other current combination chemotherapy regimens.
authors.affiliation: Department of Medicine, Section of Hematology and Oncology, University of Chicago Medical Center, University of Chicago Cancer Center and the University of Chicago Phase II Network, Chicago, IL 60637, USA. amauer@medicine.bsd.uchicago.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Mauer
authors.forename: R H
authors.initials: RH
authors.lastname: Ansari
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: S A
authors.initials: SA
authors.lastname: Krauss
authors.forename: D
authors.initials: D
authors.lastname: Taber
authors.forename: S A
authors.initials: SA
authors.lastname: Tembe
authors.forename: G T
authors.initials: GT
authors.lastname: Gabrys
authors.forename: T
authors.initials: T
authors.lastname: Cotter
authors.forename: L P
authors.initials: LP
authors.lastname: Schumm
authors.forename: L
authors.initials: L
authors.lastname: Szeto
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide