Ifosfamide and paclitaxel combinations for the treatment of advanced non-small cell lung cancer

Ifosfamide and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are among the most active agents for the treatment of non-small cell lung cancer, with single-agent response rates of 20% or greater in previously untreated patients with advanced disease. These two agents have been evaluated in several phase I and II trials of two-, three-, and four-drug regimens to determine their safety and efficacy in this patient population. Ifosfamide and paclitaxel doublets were evaluated in two phase I and II trials. Response rates ranged from 15.4% to 34%, with 1-year survival rates as high as 37%. Toxicity was acceptable, with greater degrees of myelosuppression seen with 24-hour infusion times for paclitaxel. Three-drug studies of ifosfamide, paclitaxel, and a platinum analogue have shown that these three drugs may be combined. Myelosuppression is considerable, however, and febrile neutropenia rates are high, even when growth factors are used. The addition of etoposide to the three-drug regimens has been evaluated only in phase I studies. Myelosuppression increases, and rates of febrile neutropenia as high as 26% have been reported. The lack of any suggestion of additional efficacy and the substantial toxicity suggest that four-drug combinations are not advisable.