Alteration of pemetrexed excretion in the presence of acute renal failure and effusions: Presentation of a case and review of the literature

Pemetrexed is a multitargeted antifolate approved by the Food and Drug Administration for patients with mesothelioma and non small cell lung cancer. As this agent is almost exclusively cleared by renal excretion, trials leading to its approval were conducted in patients with normal renal function. However, this cycle active agent often is administered with cisplatin to patients who may have pleural effusions and ascites. As a result, the potential for drug accumulation in effusions and for accompanying renal insufficiency is real. Recommendations for the management of pemetrexed toxicity in the presence of renal failure have not been established. A case of treatment-related acute renal failure following chemotherapy with cisplatin and pemetrexed in a patient with advanced mesothelioma and ascites is presented. Pharmacologic studies in this patient revealed persistent pemetrexed levels in ascites and plasma. This is the first time that significant accumulation of pemetrexed in ascetic fluid has been reported in the literature. Treatment with leucovorin, folate, and continuous veno-venous hemodialysis was initiated. Thymidine and carboxypeptidase were not available. Dialysis was unsuccessful in removing pemetrexed. Theoretical and practical approaches to management of similar cases are presented.