Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nelarabine (compound 506U78), a novel purine nucleoside, is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G). Nelarabine is rapidly demethoxylated in blood by adenosine deaminase to ara-G. Pre-clinical and clinical studies have demonstrated the selective cytotoxicity of ara-G to T-lineage derived cells. CALGB Protocol 59901 was a Phase II study of nelarabine in patients with systemically untreated cutaneous T-cell lymphoma (CTCL) or refractory/relapsed systemic T-cell lymphoma (STCL). The objectives were to determine response rate, remission duration and safety profile associated with nelarabine given at 1.5 g m(-2) per day on days 1, 3 and 5 as an intravenous infusion every 21 days for a minimum of two cycles and to continue up to two cycles beyond CR up to a maximum of eight cycles. Nineteen patients were enrolled in the study: 11 CTCL and eight STCL patients. Grade 3 or 4 adverse events were documented in 50% and 28%, respectively. In particular, 33% of patients experienced Grade 3 or 4 neurologic toxicities. There were two partial remissions lasting 3 months and 5.5 months, respectively. Median event-free survival was 1.2 months and median overall survival was 3 months. Due to lack of efficacy and excessive toxicity, nelarabine is not recommended as monotherapy in adult patients with CTCL and STCL at this dose schedule.
 ...
PMID:Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901. 1732 39

Nelarabine is the prodrug of 9-beta-arabinofuranosylguanine (ara-G) and is therapeutically classified as a purine nucleoside analog. Nelarabine is converted to ara-G by adenosine deaminase and transported into cells by a nucleoside transporter. Ara-G is subsequently phosphorylated to ara-G triphosphate (ara-GTP), thereby initiating the therapeutic effect by inhibiting DNA synthesis. Nelarabine has been extensively studied in regards to its pharmacokinetics, and the data have demonstrated that ara-GTP preferentially accumulates in malignant T-cells. Clinical responses to nelarabine have been demonstrated in various T-cell malignancies and appear to correlate with a relatively high intracellular concentration of ara-GTP compared to nonresponders. Therefore, this unique drug feature of nelarabine accounts for clinical utilization in treating adult and pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Neuropathy is the most predominant adverse effect associated with nelarabine and the incidence correlates with the dose administered. Myelosuppression has been observed, with thrombocytopenia and neutropenia as the most common hematologic complications. This article reviews the pharmacology, mechanism of action, and pharmacokinetic properties of nelarabine, as well as nelarabine's clinical efficacy in T-ALL, T-LBL, and other hematologic malignancies. The toxicity profile, dosage, and administration, and areas of ongoing and future research, are also presented.
 ...
PMID:Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. 2061 9


<< Previous 1 2 3 4 5 6 7