テキストサンプル
When pemetrexed and cisplatin were given on Day 1, reversible leukopenia and neutropenia with delayed fatigue defined the MTD at a dose of pemetrexed 600 mg/m2 and cisplatin 100 mg/m2. Therefore, the recommended dose was pemetrexed 600 mg/m2 and cisplatin 75 mg/m2. The administration of pemetrexed on Day 1 and cisplatin on Day 2 also showed myelosuppression as the limiting toxicity; 1 patient died from drug-related toxicity in this cohort. The recommended dose from this cohort was the same as the first. The comparison of toxicities of both schedules showed a better safety profile when pemetrexed and cisplatin were given on Day 1. This schedule was selected for further Phase 2 or 3 trials. Analysis showed that cisplatin does not alter the pharmacokinetics of pemetrexed nor does pemetrexed affect the pharmacokinetics of cisplatin. In addition, cisplatin-related hydration did not alter pemetrexed pharmacokinetics.
