Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule.
BACKGROUND
The differences in toxicity of etoposide following continuous or bolus infusion are unknown.


METHODS
We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I-III was idarubicin 8 mg/m(2) per day days 1-3, cytarabine 2000 mg/m(2) once a day days 1-6, and etoposide 1600 mg/m(2) total dose. Group IV treatment differed by cytarabine given twice daily days 1-6. Patients were randomized to etoposide as a continuous infusion days 1-6 or as a bolus infusion over 10 h on day 7.


RESULTS
Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I-III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I-III patients, 51% achieved complete remission, and 11% died from treatment-related complications.


CONCLUSIONS
The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.
Damon
Lloyd E
LE
Division of Hematology/Oncology, University of California, San Francisco, 400 Parnassus Avenue, Box 0324, San Francisco, CA 94143, USA. damonl@medicine.ucsf.edu
Johnston
Laura J
LJ
Ries
Curt A
CA
Rugo
Hope S
HS
Case
Delvyn
D
Ault
Kenneth
K
Linker
Charles A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D015255:Idarubicin