A retrospective study of the relationship between high-dose methotrexate chemotherapy-related toxicity and concomitant drugs: Non-steroidal anti-inflammatory drugs and sulfametoxazole

High-dose methotrexate (HDMTX) chemotherapy has been established as a treatment for childhood acute lymphocytic leukemia and osteosarcoma. We retrospectively studied the relationship between HDMTX-related toxicity and concomitant drugs, namely, non-steroidal antiinflammatory drugs (NSAIDs) and sulfametoxazole, in HDMTX chemotherapy. A total of 516 patients on HDMTX who had undergone therapeutic drug monitoring were enrolled in this retrospective study. On these 516 cases, 196 were eligible for efficacy analysis, and MTX concentrations at 48 hours after MTX administration were determined. The 196 cases were divided into 3 groups as follows: the control group received no concomitant drugs which can affect MTX disposition; the NSAID group was administered oral and external-use NSAIDs within 24-hours before and after MTX administration; the sulfametoxazole group was administered sulfametoxazole within 24-hours before and after MTX dosing. The concentration levels of MTX at 48 hours after HDMTX were found to be significantly increased in the NSAID group (NSAIDs: 3.61 ± 8.83μM; control: 2.52 ± 23.7μM). In conclusion, this retrospective study indicates that concomitant NSAIDs significantly increase MTX serum concentrations, and should be avoided during treatment with HDMTX.