Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG.
Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.
van der Werff Ten Bosch
J
J
Department of Pediatrics, Akademisch Ziekenhuis - VUB, Brussels, Belgium.
Suciu
S
S
Thyss
A
A
Bertrand
Y
Y
Norton
L
L
Mazingue
F
F
Uyttebroeck
A
A
Lutz
P
P
Robert
A
A
Boutard
P
P
Ferster
A
A
Plouvier
E
E
Maes
P
P
Munzer
M
M
Plantaz
D
D
Dresse
M-F
MF
Philippet
P
P
Sirvent
N
N
Waterkeyn
C
C
Vilmer
E
E
Philippe
N
N
Otten
J
J
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects*; D008727:Methotrexate / Q000008:administration & dosage; D010349:Patient Compliance; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D015203:Reproducibility of Results; D016896:Treatment Outcome
D015122:Mercaptopurine; D008727:Methotrexate