Nelarabine

Nelarabine is a prescription drug used for the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. These cancers are characterized by the uncontrolled proliferation of T-cells, a type of immune system cell. These cancers most often occur in children. Nelarabine belongs to a family of drugs known as nucleoside analogs, other members of which include vidarabine (Vira-A) and cytarabine. The nucleoside analogs function by disrupting DNA replication in rapidly dividing cells. The U.S. Food and Drug Administration approved nelarabine in November 2005.

Other Names

Nelarabine is marketed by GlaxoSmithKline under two names:

• Arranon in the United States
• Atriance in the United Kingdom and Canada

Uses

Nelarabine is used to treat adults or children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in whom at least two other chemotherapeutic drugs had been ineffective.

How Nelarabine is Taken

Nelarabine is given intravenously (IV) in a 5 mg/ml solution. The recommended adult dose is 1,500 mg/m² (per meter of body surface area) given over two hours. The treatment is given in cycles: nelarabine is given on days 1, 3, and 5 and this regimen is repeated every 21 days. The recommended dose in children is 650 mg/m² given over 1 hour daily for 5 consecutive days, repeated every 21 days.

How Nelarabine Works

In the body, nelarabine is converted to ara-G and finally ara-GTP. This last compound is similar in structure to guanine, one of the bases of DNA. Ara-GTP accumulates in cancer cells and is incorporated into growing strands of DNA. Unlike the body’s own guanosine, Ara-GTP prevents DNA replication and ultimately kills the cancer cell.

How the Body Affects Nelarabine

An enzyme called adenosine deaminase converts nelarabine into its active form. Most of nelarabine is metabolized to uric acid through a multi-step pathway. Most of a dose of nelarabine is excreted in the urine.

Benefits

Nelarabine has significant activity against malignant T-cells and appears to be an important addition to treatments of various leukemias.^[1]

Side Effects

The most common side effects of nelarabine in adults are the following:

• fatigue
• gastrointestinal (GI) disorders (nausea, diarrhea, vomiting, and constipation)
• blood disorders (anemia, low white blood cell counts, low platelet counts)
• respiratory disorders (cough and shortness of breath)
• nervous system disorders (sleepiness and dizziness)
• high fever

Risks and Precautions

Nelarabine may cause severe, persistent nervous system problems such as:

• tingling
• numbness
• lack of coordination (e.g., unsteadiness when walking)
• weakness when rising from a low chair or climbing stairs
• seizures
• extreme drowsiness

Drug Interactions

No significant drug interactions have been reported with nelarabine.

Research

A multicenter trial examined the effectiveness of nelarabine in 13 patients with T-cell lymphoblastic lymphoma and 13 patients with acute T-cell lymphoblastic leukemia.^[2] Complete remission was seen in 31% of patients and the overall response rate was 41%. Less than 40% of patients had experienced low white blood cell counts, which was the most common side effect.

References

1. ↑ Kisor DF.Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias. Ann Pharmacother. 2005 Jun;39(6):1056-63. Review. [http:pubmed.gov/15870141 Abstract]
2. ↑ DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42. Abstract | Full Text | PDF

External Links

FDA: Patient Information Sheet