Phase II study of docetaxel and ifosfamide combination chemotherapy in non-small-cell lung cancer patients failing previous chemotherapy with or without paclitaxel

[[abstract]]Docetaxel has shown activity in the treatment of non-small-cell lung cancer (NSCLC) that has failed previous chemotherapy. Ifosfamide is an active alkylating agent used in the first-line treatment of NSCLC. We conducted a phase 11 study of docetaxel and ifosfamide chemotherapy in two groups (one with and one without previous paclitaxel treatment) of NSCLC patients who had failed previous chemotherapy, to assess the response and toxicity of this combination chemotherapy. Fifty patients were enrolled from June 2000 to December 2001, including 26 patients treated with paclitaxel-containing agents and 24 patients who had never been treated with paclitaxel. Treatment consisted of docetaxel 60 mg/m(2) and ifosfamide 3 g/m(2) intravenous infusion on day I of every 3 weeks. Two hundred and thirty-eight cycles of treatment were given, with a median of 5 cycles (range, 1-8 cycles). All patients were evaluable for toxicity profile and response rate. The major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 40 patients (80%) during treatment. Febrile neutropenia occurred in 7 patients (14%). Grade 3 anemia occurred in 2 patients. The majority of patients needed a decrease in the treatment dose due to grade 4 or febrile neutropenia. Interstitial pneumonitis occurred in 3 patients, leading to the death of two. Other toxicities were few and mild in severity. After two cycles of treatment, 5 patients (10%) had a partial response (95% confidence interval 1.7-18.3%), including 2 patients previously treated with paclitaxel and 3 who had not received this treatment. More patients who had been previously treated with paclitaxel suffered from progressive disease than among those who had never been treated with paclitaxel (P = 0.049). The median time to disease progression was 5 months and the median survival was 8.2 months. Median survival was 7.6 and 8.7 months, respectively, in patients with and without previous paclitaxel treatment (P = 0.56). Median survival was 8.7 and 7.6 months in patients receiving docetaxel and ifosfamide as second- and third-line chemotherapy, respectively (P = 0.327). In conclusion, docetaxel and ifosfamide salvage chemotherapy produces a relatively low response rate, low dose intensity, and higher proportion of severe neutropenia in NSCLC. Physicians should be alert to the potential of interstitial pneumonitis. Nevertheless, median survival was of a reasonable duration