title: How much is too much? Folinic acid rescue dose in children with acute lymphoblastic leukaemia.
abstract: The effect of folinic acid rescue dose on the event-free survival of 71 children with acute lymphoblastic leukaemia was examined in a retrospective clinical study. All patients, diagnosed between 1 January 1980 and 1 January 1989, were treated according to the Norwegian Pilot protocol which included eight courses of high dose (6-8 g/m2/24 h intravenous infusion) methotrexate. Following the infusion, a uniform dose of 75 mg (at 36 h after the beginning of the drug infusion) and 15 mg (at 39-106 h) folinic acid rescue was administered to all patients, at predetermined intervals. The uniformity of the rescue dose resulted in distribution of dosages in the range of 38-140 mg/m2 and 7.5-28 mg/m2 for the different periods, respectively, when the dose was recalculated on the basis of the body surface area of the individual patients. The event-free survival of children receiving less or more than 15 mg/m2 (75 mg/m2) rescue dose was compared. Although no significant difference was found, a tendency was observed for a lower risk of relapse in patients receiving less folinic acid. No major methotrexate-related toxicity was observed in the group of patients receiving the lower dose of rescue. These observations suggest that the reduction of folinic acid rescue dose below the generally accepted 12-15 mg/m2 dose may increase the efficacy of high-dose methotrexate therapy while still remaining safe in preventing treatment-related toxicity. Prospective, randomised clinical trials are needed to examine the role of rescue as a determinant of effective exposure to methotrexate in patients receiving high-dose methotrexate treatment.
authors.affiliation: Department of Pediatric Oncology, Semmelweis Medical School, Budapest, Hungary.
authors.forename: J D
authors.initials: JD
authors.lastname: Borsi
authors.forename: F
authors.initials: F
authors.lastname: Wesenberg
authors.forename: T
authors.initials: T
authors.lastname: Stokland
authors.forename: P J
authors.initials: PJ
authors.lastname: Moe
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D002955:Leucovorin; D008727:Methotrexate