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A phase I/II study of intensive dose escalation of cytarabin in combinaton with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia

journal contribution
posted on 2023-05-16, 11:34 authored by Raymond Lowenthal, Bradstock, KF, Matthews, JP, Bishop, JF, Juneja, S, Cobcroft, R, Eliadis, P, Enno, A, Gill, D, Herrmann, RP, Manoharan, A, Page, FJ, Rooney, KF, Rosenfeld, D, Seldon, M, Taylor, KM, Wolf, MM, Young, GAR
To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ('ICE') for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.

History

Publication title

Leukemia and Lymphoma

Volume

34

Issue

5-6

Pagination

501-510

ISSN

1042-8194

Department/School

Tasmanian School of Medicine

Publisher

Harwood Academic

Place of publication

Netherland

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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