Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group. J Pediatr Hematol Oncol 2014 Jul;36(5):353-61
Date
03/13/2014Pubmed ID
24608079Pubmed Central ID
PMC4120865DOI
10.1097/MPH.0000000000000131Scopus ID
2-s2.0-84903760629 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).
PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.
RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.
CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.
Author List
Tower RL, Jones TL, Camitta BM, Asselin BL, Bell BA, Chauvenet A, Devidas M, Halperin EC, Pullen J, Shuster JJ, Winick N, Kurtzberg JAuthor
Richard L. Tower MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic Combined Chemotherapy ProtocolsAsparaginase
Child
Cytarabine
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Humans
Male
Methotrexate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Remission Induction
Risk Factors
Survival Rate
Teniposide
