A phase I trial of a single high dose of idarubicin combined with high-dose cytarabine as induction therapy in relapsed or refractory adult patients with acute lymphoblastic leukemia Journal Article

  

Authors:	Weiss, M. A.; Drullinsky, P.; Maslak, P.; Scheinberg, D.; Golde, D. W.
Article Title:	A phase I trial of a single high dose of idarubicin combined with high-dose cytarabine as induction therapy in relapsed or refractory adult patients with acute lymphoblastic leukemia
Abstract:	Relapsed or refractory adult acute lymphoblastic leukemia (ALL) carries a grave prognosis. The most promising strategy for curing these patients is through re-induction chemotherapy followed by successful allogeneic transplant. We studied a new high-dose induction regimen inorder to improve the outcome for these patients. Eighteen adult patients with relapsed/refractory ALL were treated on a phase I study of high-dose cytarabine combined with a single escalating dose of idarubicin. Five patients had primary refractory disease and 13 were treated in refractory relapse. Nine patients (50%) had Ph+ ALL. The induction regimen was cytarabine 3 g/m2/day intravenously days 1-5 and idarubicin as a single intravenous dose on day 3. G-CSF 5 μg/kg subcutaneously every 12 h was started on day 7. The initial idarubicin dose was 20 mg/m2 with dose escalations of 10 mg m2. Cohorts of three patients were treated at each idarubicin dose level. Unacceptable toxicity was encountered at 50 mg/m2 with one death from infection and one death from cardiotoxicity in a patient with significant prior anthracycline exposure. There were no instances of grade 4 non-hematologic toxicity encountered at idarubicin doses of 20 mg/m2, 30 mg/m2, or 40 mg/m2. The data suggest a dose-response relationship for increasing doses of idarubicin with 0/3 complete responses (CR) at 20 mg/m2, 1/3 CR at 30 mg/m2, and 7/12 (58%) CR at idarubicin doses ≤ 40 mg/m2. We conclude that concomitant administration of cytarabine 3 g/m2/day x 5 and high-dose idarubicin at 40 mg/m2 as a single dose on day 3 can be administered safely to patients with refractory and relapsed ALL.
Keywords:	adult; clinical article; middle aged; clinical trial; diarrhea; dose response; cytarabine; neurotoxicity; infection; liver toxicity; nephrotoxicity; bleeding; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; allogenic bone marrow transplantation; acute lymphoblastic leukemia; cardiotoxicity; drug toxicity; phase 1 clinical trial; idarubicin; granulocyte colony stimulating factor; intravenous drug administration; leukemia, lymphocytic, acute; subcutaneous drug administration; humans; prognosis; human; male; female; priority journal; article; relapsed refractory adult all
Journal Title:	Leukemia
Volume:	12
Issue:	6
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	1998-06-01
Start Page:	865
End Page:	868
Language:	English
PUBMED:	9639412
PROVIDER:	scopus
DOI:	10.1038/sj.leu.2401058
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031861959&partnerID=40&md5=c0de1fedcb714e71aa50915a6ed5174a
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

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