Dose Escalation and Pharmacokinetic Study of Carboplatin plus Pernetrexed for Elderly Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer: Kumamoto Thoracic Oncology Study Group Trial 1002

Objectives: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (>= 70-year-old) chemotherapy-naive patients with advanced nonsquannous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. Methods: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. Results: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. Conclusions: For elderly chemotherapy-naive patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities. (C) 2014 S. Karger AG, Basel