Author:
Santana V M,Mirro J,Kearns C,Schell M J,Crom W,Blakley R L
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.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
145 articles.
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