Abstract | BACKGROUND: METHODS: The authors present a case of a 48-year-old male with Philadelphia chromosome (Ph) positive CML and T-cell lymphoid BP after 17 months in the chronic phase. RESULTS: Plasma pharmacokinetic studies after an infusion of GW506U78 at a dose of 40 mg/kg showed GW506U78 concentrations of 60 microM, and a peak ara-G concentration of 260 microM in the plasma. Cellular ara-G triphosphate ( ara-GTP) concentration in the peripheral blood T-lymphoblasts was 80 microM at the end of GW506U78 infusion and reached a maximum of 150 microM. The patient achieved a complete response that lasted 13 months. Severe neurotoxicity related to GW506U78 was observed. CONCLUSIONS:
GW506U78 showed antileukemic activity against Ph positive T-cell BP CML. Neurotoxicity was dose-limiting in this patient. Treatment with GW506U78 and modulation of ara-GTP concentrations are therapeutic strategies that require further exploration in T-cell malignancies. Investigation of other dosing schedules may limit neurotoxicity.
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Authors | A Aguayo, J E Cortes, H M Kantarjian, M Beran, V Gandhi, W Plunkett, J Kurtzberg, M J Keating |
Journal | Cancer
(Cancer)
Vol. 85
Issue 1
Pg. 58-64
(Jan 01 1999)
ISSN: 0008-543X [Print] United States |
PMID | 9921974
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
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Chemical References |
- Antineoplastic Agents
- Arabinonucleosides
- Arabinonucleotides
- nelarabine
- 9-beta-D-arabinofuranosylguanosine 5'-triphosphate
- Guanosine Triphosphate
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Topics |
- Antineoplastic Agents
(pharmacokinetics, therapeutic use)
- Arabinonucleosides
(pharmacokinetics, therapeutic use)
- Arabinonucleotides
(blood)
- Blast Crisis
(drug therapy)
- Guanosine Triphosphate
(analogs & derivatives, blood)
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(drug therapy, pathology)
- Male
- Middle Aged
- Remission Induction
- T-Lymphocytes
(pathology)
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