Safety of dose-reduced pemetrexed in patients with renal insufficiency

J Oncol Pharm Pract. 2019 Jul;25(5):1125-1129. doi: 10.1177/1078155218780507. Epub 2018 Jun 5.


Purpose: Pemetrexed has been shown to be effective in the treatment of advanced and metastatic nonsquamous nonsmall cell lung cancer. In this population, renal insufficiency is common; however, pemetrexed is not recommended in patients with a creatinine clearance (CrCl) < 45 ml/min due to increased myelosuppression reported in phase I trials. The primary objective of this study is to determine the safety of dose-reduced pemetrexed in patients with a CrCl < 45 ml/min.

Methods: This is a retrospective case series describing the incidence of grade 3 or higher toxicity in patients with CrCl < 45 ml/min treated with dose-reduced pemetrexed at The James Cancer Hospital and Solove Research Institute at The Ohio State University.

Results: A total of eighteen patients were included. Seven (39%) patients experienced a grade ≥ 3 toxicity. Only 18% of administrations led to a grade ≥ 3 toxicity. Four (22%) patients had grade ≥ 3 hematologic toxicity; three of which were receiving concomitant platinum agents. The fourth patient had a CrCl < 30 ml/min. No patients receiving single-agent pemetrexed with a CrCl > 30 ml/min experienced grade ≥ 3 hematologic toxicity.

Conclusions: Dose-adjusted pemetrexed may be cautiously administered to patients with a CrCl between 30 and 45 ml/min. Extra caution is warranted in patients receiving concomitant chemotherapy with a platinum agent as well as those with a CrCl < 30 ml/min. Pemetrexed in combination with a platinum agent should not be routinely recommended for patients with a CrCl < 30 ml/min.

Keywords: Nonsmall cell lung cancer; pemetrexed; renal dysfunction.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Pemetrexed / administration & dosage*
  • Pemetrexed / adverse effects
  • Renal Insufficiency / complications*
  • Retrospective Studies


  • Pemetrexed