Toxicity and response of pemetrexed plus carboplatin or cisplatin with concurrent chest radiation therapy for patients with locally advanced non-small cell lung cancer: A phase i trial

Introduction: Pemetrexed is an effective and a tolerable drug in advanced non-small cell lung cancer (NSCLC). This study sought to ascertain maximum tolerated dose (MTD) and phase II dose of carboplatin or cisplatin given with pemetrexed and concurrent chest radiation therapy (CRT) in locally advanced NSCLC. Methods: Eligible, previously untreated patients were enrolled with the initial intent of establishing the MTD of both weekly cisplatin or carboplatin combined with pemetrexed 500 mg/m² every 3 weeks and concurrent CRT in an alternating, two arm, phase I trial. Secondary objectives included response rate and toxicity. The protocol was subsequently amended to establish the safety of planned phase II doses of cisplatin or carboplatin combined with pemetrexed 500 mg/m given every 3 weeks × 3 cycles with CRT. Results: Patients received pemetrexed combined with carboplatin area under curve = 2 (n = 9), cisplatin 30 mg/m² (n = 9), or cisplatin 75 mg/m² (n = 4). One dose-limiting toxicity occurred in both the carboplatin and in the cisplatin 30 mg/m² cohorts. No dose-limiting toxicities occurred in the cisplatin 75 mg/m² cohort. Because these are standard doses without radiation therapy in lung cancer, there was no further dose escalation. Partial response rates were 11% (carboplatin) and 46% (combined cisplatin). Stable disease rates were 33% (carboplatin) and 46% (combined cisplatin). Two patients receiving carboplatin experienced disease progression. Conclusions: The MTD of cisplatin combined with pemetrexed was not reached. Based on these and Cancer and Leukemia Group B 30407 results, pemetrexed with either carboplatin or cisplatin at full systemic doses with CRT seems to be well tolerated. A multicenter, randomized phase II trial of both regimens is underway.