Continuous response despite reduced dose of trametinib as single agent in an adolescent with a relapsed disseminated pediatric low-grade glioma KIAA1549-BRAF fusion positive: a case report and review of the literature.

Dissemination in pediatric low-grade glioma may occur in about 4%-10% of patients according to retrospective cohort studies. Due to its low incidence, there is no consensus on treatment for these patients. According to the constitutional activation of the MAPK/ERK pathway in these tumors, MEK inhibitors such as trametinib have been used successfully in the relapsed setting. Skin toxicity is frequent in patients receiving trametinib, normally mild to moderate, but sometimes severe, needing to discontinue the drug, limiting the efficacy in the tumor. There is not much information in the literature regarding whether reducing the dose of trametinib is able to maintain efficacy while, at the same time, decreasing toxicity. Here, we present an adolescent, with severe skin toxicity, whose trametinib dose was reduced by 50% and efficacy on the tumor continued while skin toxicity significantly decreased.

Use of glucarpidase (carboxypeptidase-G2) in pediatric cancer patients: 11-year experience of a tertiary center.

Methotrexate is an essential drug in the treatment of childhood cancer that is not exempt from toxicities. Glucarpidase is a drug used to reduce the toxic concentration of plasma methotrexate in patients with delayed elimination or at risk of toxicity. We describe the characteristics of a cohort of pediatric patients that received glucarpidase and analyze its role in the treatment of toxicity induced by high doses of methotrexate (HDMTX). Retrospective observational study of all pediatric cancer patients who received glucarpidase between 2012 and 2022 at a single center. Fifteen patients were treated with a single dose of glucarpidase, eleven of them presented with acute lymphoblastic leukemia and received HDMTX at 5 g/m2 in 24-hour infusion. In eight patients, glucarpidase was administered during the first cycle of HDMTX. The indication in thirteen cases was acute renal failure with delayed elimination of plasma methotrexate. The median maximum creatinine was 1.22 mg/dl (0.68 2.01 mg/dl), with a median increase over its baseline level of 313%. All patients normalized renal function after glucarpidase administration, with a median methotrexate excretion time of 193 hours (42-312 hours). No grade ≥2 adverse events derived from carboxypeptidase administration. Eleven patients received new doses of HDMTX in subsequent cycles, without new episodes of serious toxicity. The use of glucarpidase is effective and safe in the treatment of acute renal failure and methotrexate elimination delay in pediatric cancer patients. Further HDMTX doses may be prescribed without additional toxicities.