The Correlation Between Dose of Folinic Acid and Neurotoxicity in Children and Adolescents Treated for Osteosarcoma With High-dose Methotrexate (HDMTX): A Neuropsychological and Psychosocial Study

Background: This study has been performed to examine the currently used doses of folinic acid (FA) and to determine the importance of the dose of FA in preventing subtle neurotoxicity. Thirty osteosarcoma patients were an appropriate population studied as they have no intrinsic neurological involvement. The neuropsychological and psychosocial status was tested in 2 groups of patients treated with similar protocols containing repeated doses of high-dose methotrexate, but different doses of FA. The patients received 300 to 600 mg/m(2) or 120 to 250 mg/m(2) FA in their protocols. Methods: Eighteen tests or subtests of neuropsychological assessment were tested. Results: Eleven of 18 tests were significant at the P = 0.025 level favoring the group treated with high dose of FA. There were no clear results in the psychosocial measures with only a single measure of self-esteem (understanding) being significantly higher (P = 0.024) in the group treated with high dose of FA, other measures had no statistical significance. Conclusions: A correlation between a higher dose of FA after high-dose methotrexate and a better neuropsychological status was clearly shown. The doses of FA used in the low FA group, 120 to 250 mg/m(2), were similar to those used by several groups treating children with leukemia; some have used even lower doses and report gross neurotoxicity.