Japanese Journal of Clinical Oncology, Vol 27, Issue 3 146-153, Copyright © 1997 by Foundation for Promotion of Cancer Research
K Tobinai, M Ogura, T Hotta, Y Kobayashi, M Narabayashi, R Suzuki, T Kinoshita, M Kozuru, N Uike and Y Ohashi
Cladribine (2-chlorodeoxyadenosine;) is a purine analogue with clinical
activity against hairy cell leukemia, chronic lymphocytic leukemia and
indolent lymphoma. To clarify the toxicity profiles of cladribine, we
conducted a phase I and pharmacological study of cladribine with a schedule
of seven-day continuous intravenous infusion every 28 days up to a maximum
of three cycles. We enrolled 10 previously-treated patients with various
lymphoid malignancies. No dose-limiting toxicity (grade 4 hematologic
and/or grade 3 or more non-hematologic) was observed in the three patients
who received 0.06 mg/kg/day (Level 1). Of the seven patients who received
0.09 mg/kg/day (Level 2), one patient developed grade 4 hypoxemia and grade
4 thrombocytopenia, and another developed grade 4 neutropenia. Of the seven
patients treated at Level 2, one with cutaneous T-cell lymphoma attained
complete remission, and one with mantle cell lymphoma, one with chronic
lymphocytic leukemia and one with adult T-cell leukemia-lymphoma attained
partial remission. A pharmacokinetic analysis of the seven patients without
leukemic cells showed that their area under the concentration versus time
curves of plasma cladribine increased dose-dependently from 2661.3 +/-
300.4 nM x h at Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n =
4) (P = 0.034). We conclude that the recommended phase II dose of
cladribine (0.09 mg/kg/day as a seven-day continuous i.v. infusion) in
Caucasian patients can be safely administered to Japanese patients. The
encouraging results prompted us to plan subsequent phase II studies of
cladribine against adult T-cell leukemia-lymphoma, hairy cell leukemia and
indolent lymphoma.
CASE REPORTS
Phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies. Cladribine Study Group
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
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