2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.

Abstract

PURPOSE:

The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia.

PATIENTS AND METHODS:

Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients.

RESULTS:

Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L).

CONCLUSION:

2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.

• Authors: V M Santana, J Mirro Jr, C Kearns, M J Schell, W Crom, R L Blakley
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 10 Issue 3 Pg. 364-70 (Mar 1992) ISSN: 0732-183X [Print] United States
• PMID: 1346800 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Deoxyadenosines
• 2-Chloroadenosine
• Cladribine

Topics

• 2-Chloroadenosine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Acute Disease
• Adolescent
• Adult
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Bone Marrow Transplantation
• Child
• Child, Preschool
• Cladribine
• Combined Modality Therapy
• Deoxyadenosines (pharmacokinetics, therapeutic use)
• Drug Evaluation
• Female
• Humans
• Infusions, Intravenous
• Leukemia, Myeloid (blood, drug therapy, surgery)
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (blood, drug therapy, surgery)
• Recurrence
• Regression Analysis
• Remission Induction