Phase I and Pharmacokinetic Study of Pemetrexed plus Cisplatin in Chemonaive Patients with Locally Advanced or Metastatic Malignant Pleural Mesothelioma or Non–Small Cell Lung Cancer

Abstract

Pemetrexed with vitamin supplementation was safe and well tolerated at higher doses than the currently established 500 mg/m(2) + 75 mg/m(2) cisplatin. Based on this study, the recommended dose would be 800 mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. However, recent studies showed a lack of improved efficacy for 900 or 1,000 mg/m(2) single-agent pemetrexed versus 500 mg/m(2) and a lack of PK/pharmacodynamic exposure-response relationship for the pemetrexed/cisplatin combination across pemetrexed exposures corresponding to this dose range. Based on currently available evidence, we recommend retaining the established dose.