Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951.
The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.
De Moerloose
Barbara
B
Department of Pediatric Hematology-Oncology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium. barbara.demoerloose@ugent.be
Suciu
Stefan
S
Bertrand
Yves
Y
Mazingue
Françoise
F
Robert
Alain
A
Uyttebroeck
Anne
A
Yakouben
Karima
K
Ferster
Alice
A
Margueritte
Geneviève
G
Lutz
Patrick
P
Munzer
Martine
M
Sirvent
Nicolas
N
Norton
Lucilia
L
Boutard
Patrick
P
Plantaz
Dominique
D
Millot
Frederic
F
Philippet
Pierre
P
Baila
Liliana
L
Benoit
Yves
Y
Otten
Jacques
J
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011239:Prednisolone / Q000008:administration & dosage; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D000305:Adrenal Cortex Hormones; D014750:Vincristine; D003907:Dexamethasone; D011239:Prednisolone
Lancet. 1995 Jan 21;345(8943):143-8
7823668
J Clin Oncol. 1996 Mar;14(3):911-8
8622039
Lancet Oncol. 2008 Mar;9(3):257-68
18308251
Eur J Cancer. 2007 Nov;43(17):2532-6
17702568
Blood. 2003 May 15;101(10):3809-17
12531809
Med Pediatr Oncol. 1993;21(9):655-60
8412999
J Clin Oncol. 2008 Jan 10;26(2):283-9
18182669
Lancet. 2007 Jan 13;369(9556):123-31
17223475
Leukemia. 2000 Dec;14(12):2247-56
11187916
Blood. 2010 Jul 8;116(1):36-44
20407035
Leukemia. 2000 Dec;14(12):2257-66
11187917
Br J Haematol. 2005 Jun;129(6):734-45
15952999
Haematol Blood Transfus. 1990;33:439-50
2182435
Blood. 1999 May 1;93(9):2817-23
10216075
J Clin Oncol. 1991 Jun;9(6):1012-21
2033414
Cancer. 1981 Jan 1;47(1):207-14
7459811
Med Pediatr Oncol. 1991;19(4):269-75
2056971
N Engl J Med. 1998 Aug 27;339(9):591-8
9718378
Arch Dis Child. 1991 Apr;66(4):462-6
2031601
Haematol Blood Transfus. 1990;33:459-66
2182437
Lancet. 1996 Jun 29;347(9018):1783-8
8667921
Cancer. 1972 Dec;30(6):1480-7
4509104