Phase I trial of dose-escalated paclitaxel and carboplatin in combination with ifosfamide and filgrastim: preliminary results.

The ongoing phase I study reported here sought to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin when given at specific times in combination with ifosfamide, mesna, and filgrastim. Patients in the trial included those with non-small cell lung cancer (three), breast cancer (two), metastatic adenocarcinomas of unknown primary site (two), prostate cancer (one), angioimmunoblastic lymphadenopathy (one), and mesothelioma (one). The median age of these 10 patients was 48 years (age range, 34 to 75 years) and none had received chemotherapy previously. Of the 12 patients who entered the study, 10 are eligible for analyses of toxicity and response. The only grade 4 toxicity observed was hematologic. One episode of neutropenic fever occurred in the 43 treatment cycles delivered so far, one patient experienced an ifosfamide-related change in mental state, and two patients developed reversible renal tubular acidosis. No other significant neurologic or renal toxicities have been observed. At dose level 1, the cycle-6 doses were delayed in one patient, and another patient required a 50% reduction of the ifosfamide dose during cycle 4 due to mental status change. At dose level 2, there were no dose reductions or delays due to side effects, although one patient withdrew due to disease progression. At dose level 3, dose delays only were required in six of 15 cycles. The response rate was 100%; four patients achieved a complete response (40%) and six a partial response (60%). This regimen appears to be tolerable and active at the dose levels completed thus far, with minimal nonhematologic toxicities.