Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children's Cancer Group.
The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.
UCLA Medical Center, USA.
S A
SA
Feig
M M
MM
Ames
H N
HN
Sather
L
L
Steinherz
J M
JM
Reid
M
M
Trigg
T W
TW
Pendergrass
P
P
Warkentin
M
M
Gerber
M
M
Leonard
W A
WA
Bleyer
R E
RE
Harris
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012008:Recurrence
D000903:Antibiotics, Antineoplastic; D015255:Idarubicin; D003630:Daunorubicin