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

Abstract

Objectives: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous 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/m²) 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/m² 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-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m² 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. © 2014 S. Karger AG, Basel

nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC

“…To date, the median OS values reported with nab -paclitaxel/carboplatin treatment of elderly patients in this study and in the elderly subset of the phase 3 trial are among the longest reported in elderly patients with advanced NSCLC. It should be noted that studies of pemetrexed/carboplatin have indicated that a carboplatin dose of AUC 5 may be more tolerable in this population ( 10 , 11 ). However, other large studies of taxane-based doublets have routinely examined carboplatin AUC 6 in elderly patients ( 4 , 5 , 9 ).…”