Predictive factors associated with pemetrexed acute toxicity

Purpose Pemetrexed has shown efficacy as monotherapy or in combination with platinum salts in the treatment of non-small cell lung cancer and mesothelioma. However, severe hematological toxicities induced by pemetrexed-based chemotherapy have been observed. Some studies have suggested that drug interactions may be associated with pemetrexed toxicity. The objective of this study was to determine predictive factors, including drug interactions, associated with pemetrexed toxicity. Methods This retrospective open monocentric study included patients consecutively treated with pemetrexed after a multidisciplinary risk assessment. Patients who experienced toxicity of grade 3 or 4 according to the Common Terminology Criteria for Adverse Events v5.0, or a grade 2 leading to a change in management, during the first four courses of pemetrexed, were assigned to the early limiting toxicities (ELT) group. Univariate and multivariable logistic regression models were used to test the association variables with the occurrence of ELT. Results Seventy-four patients were included in this study (median age: 67 years, with non-small cell lung cancer adenocarcinoma (88%), mesothelioma (7%), or others (5%). Thirty-six patients (49%) were assigned to the ELT group (27 grades 3 and 4; 9 grade 2 with management modification). Three baseline factors were associated with pemetrexed ELT in univariate and multivariate analysis: cystatin clearance ( p = 0.0135), albumin level ( p = 0.0333), and proton pump inhibitors use ( p = 0.035). Conclusion To conclude, ELT induced by pemetrexed-based treatments occur frequently in cancer patients in a real-world setting. A pretherapeutic assessment before pemetrexed initiation should include three major checkpoints: use of proton pump inhibitors, sarcopenia, and denutrition evaluation.