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About ARRANON
Drug Rationale [2]
ARRANON is a pro-drug of the cytotoxic deoxyguanosine analogue, 9-β-D-arabinofuranosylguanine (ara-G). ARRANON was designed to mimic some properties of purine nucleoside phosphorylase (PNP) deficiency.
Mechanistic studies determined the differential sensitivity was due to the inherently greater phosphorylation of dGuo in T cells and a more rapid catabolism of deoxyguanosine triphosphate (dGTP) in B cells, which resulted in a T-cell selective accumulation of dGTP and dGTP-directed inhibition of DNA synthesis and cell death.
Like dGuo in patients with PNP deficiency, the analog ara-G demonstrates T-cell specific cytotoxicity associated with greater accumulation and more prolonged retention of the cytotoxic triphosphate, ara-GTP. Greater accumulation of ara-GTP is also evident in primary T-acute lymphoblastic leukemia (T-ALL) cells compared with B-lymphoid or myeloid leukemia cells.
Ara-G is relatively resistant to phosphorolysis by PNP, which makes ara-G an excellent candidate clinical agent for T-cell malignancies.
Indication
ARRANON is indicated for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.
Important Safety Information
ARRANON® (nelarabine) injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. This product is for intravenous use only.
Neurologic Events: Severe neurologic events have been reported with the use of ARRANON. These events have included altered mental states including severe somnolence, central nervous system effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis. There have also been reports of events associated with demyelination, and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome.
Full recovery from these events has not always occurred with cessation of therapy with ARRANON. Close monitoring for neurologic events is strongly recommended, and ARRANON should be discontinued for neurologic events of NCI Common Toxicity Criteria grade 2 or greater.
In clinical studies of ARRANON, hematologic toxicity was the most common grade 3 (moderate) or 4 (severe) adverse event. For a complete list and incidence of adverse events: pediatric patients; adult patients. Hematologic toxicity included neutropenia, thrombocytopenia, anemia, febrile neutropenia, or neutropenia with infection.
Other common toxicities included laboratory abnormalities including increased transaminases, gastrointestinal toxicity, fatigue, and asthenia.
Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation may be at increased risk for neurologic adverse events.
Women of child-bearing potential should be advised to avoid becoming pregnant while receiving treatment with ARRANON.
Appropriate measures (e.g., hydration, urine alkalinization, and prophylaxis with allopurinol) must be taken to prevent hyperuricemia of tumor lysis syndrome.
Nursing should be discontinued in women who are receiving therapy with ARRANON.
Because the risk of adverse reactions to this drug may be greater in patients with severe renal impairment (CLcr <30 mL/min), these patients should be closely monitored for toxicities when treated with ARRANON.
Because the risk of adverse reactions to this drug may be greater in patients with severe hepatic impairment (bilirubin >3.0 mg/dL), these patients should be closely monitored for toxicities when treated with ARRANON.
Prescribing Information for ARRANON | Important Safety Information | Patient Information Leaflet
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