Abstract | PURPOSE: PATIENTS AND METHODS: This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/ lymphoma study groups and a Japanese group. RESULTS: Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001). CONCLUSION: The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m2 in a 3-hour infusion without IT therapy.
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Authors | Laurence Brugières, Marie-Cécile Le Deley, Angelo Rosolen, Denise Williams, Keizo Horibe, Grazyna Wrobel, Georg Mann, Jozsef Zsiros, Anne Uyttebroeck, Ildiko Marky, Laurence Lamant, Alfred Reiter |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 27
Issue 6
Pg. 897-903
(Feb 20 2009)
ISSN: 1527-7755 [Electronic] United States |
PMID | 19139435
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimetabolites, Antineoplastic
- Methotrexate
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Topics |
- Adolescent
- Antimetabolites, Antineoplastic
(administration & dosage)
- Child
- Child, Preschool
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Humans
- Infant
- Injections, Spinal
- Lymphoma, Large B-Cell, Diffuse
(drug therapy, pathology)
- Male
- Methotrexate
(administration & dosage)
- Treatment Outcome
- Young Adult
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