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High-dose etoposide and cyclophosphamide without bone marrow
transplantation for resistant hematologic malignancy
RA Brown, RH Herzig, SN Wolff, D Frei-Lahr, L Pineiro, BJ Bolwell, JN Lowder, EA Harden, KR Hande and GP Herzig
Department of Medicine, Washington University, St Louis, MO.
Seventy-five patients with resistant acute leukemia or lymphoma received
high-dose cyclophosphamide and etoposide to explore the activity of this
combination in resistant hematologic malignancies, and to determine the
maximum doses of these drugs that can be combined without bone marrow
transplantation. Etoposide was administered over 29 to 69 hours by
continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2.
Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days
total 150 to 200 mg/kg ideal body weight). At all dose levels
myelosuppression was severe but reversible. Mucosal toxicity was
dose-limiting with the maximum tolerated dose level combining etoposide 4.2
g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion
produced stable plasma levels that were lower than would be achieved after
administration by short intravenous infusion, and this could explain our
ability to escalate etoposide above the previously reported maximum
tolerated dose. There were 28 complete (35%) and 12 partial (16%)
responses. Median duration of complete response (CR) was 3.5 months (range
1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia
(AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine
arabinoside resistance. We conclude that bone marrow transplantation is not
required after maximum tolerated doses of etoposide and cyclophosphamide.
This regimen is active in resistant hematologic neoplasms, and the
occurrence of CR in patients with high-dose cytosine arabinoside-resistant
AML indicates a lack of complete cross-resistance between these regimens.
Volume 76,
Issue 3,
pp. 473-479,
08/01/1990
Copyright © 1990 by The American Society of Hematology
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