Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells.
Abstract | PURPOSE: PATIENTS AND METHODS: RESULTS: Seven patients had a partial or complete response, six of whom had indolent leukemias. The disease in four responders had failed prior fludarabine therapy. The median peak intracellular concentrations of ara-GTP were significantly different (P =.001) in responders (890 micromol/L, n = 6) and nonresponders (30 micromol/L, n = 6). Also, there was a direct relationship between the peak fludarabine triphosphate and ara-GTP in each patient (r = 0.85). The cellular elimination of ara-GTP was slow (median, 35 hours; range, 18 to > 48 hours). The ratio of ara-GTP to its normal counterpart, deoxyguanosine triphosphate, was higher in each patient (median, 42; range, 14 to 1,092) than that of fludarabine triphosphate to its normal counterpart, deoxyadenosine triphosphate (median, 2.2; range, 0.2 to 27). CONCLUSION:
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Authors | V Gandhi, W Plunkett, S Weller, M Du, M Ayres, C O Rodriguez Jr, P Ramakrishna, G L Rosner, J P Hodge, S O'Brien, M J Keating |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 19
Issue 8
Pg. 2142-52
(Apr 15 2001)
ISSN: 0732-183X [Print] United States |
PMID | 11304766
(Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Arabinonucleosides
- Arabinonucleotides
- Biomarkers
- nelarabine
- 9-beta-D-arabinofuranosylguanosine 5'-triphosphate
- Guanosine Triphosphate
- Vidarabine
- fludarabine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Arabinonucleosides
(administration & dosage, pharmacokinetics, pharmacology)
- Arabinonucleotides
(analysis, metabolism)
- Biomarkers
(analysis)
- Female
- Guanosine Triphosphate
(analogs & derivatives, analysis, metabolism)
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(drug therapy)
- Leukemia, Prolymphocytic
(drug therapy)
- Male
- Middle Aged
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(drug therapy)
- Prognosis
- Treatment Outcome
- Vidarabine
(administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology)
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