Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer

Background: To find the maximum tolerated dose for ifosfamide in combination with paclitaxel and carboplatin in small-cell lung cancer patients (SCLC), who are resistant to cyclophosphamide, doxorubicin and etoposide (CDE).Patients and methods: Different dose schedules of ifosfamide were combined with fixed doses of paclitaxel 175 mg/m(2) and carboplatin AUC 6 mg/ml . min. Included were 30 patients, with a median age of 60 years, and median time off prior cytotoxic treatment of 8 weeks. All patients were previously treated with CDE and 11 had received re-induction CDE.Results: Dose limiting toxicity of our schedule was persistent thrombocytopenia. None of the patients developed neutropenic fever. Non-haematological toxicity was mild, although two treatment-related deaths occurred. Fifty-four percent of patients had a partial response and median survival time was twenty-five weeks.Conclusions: The maximum tolerated dose of this combination for patients with resistant SCLC is ifosfamide 2000 mg/m(2) in combination with paclitaxel 175 mg/m(2) and carboplatin AUC 6 mg/ml . min administered on the first day of a 21-day cycle.