Pentostatin 2Deoxycoformycin

Pentostatin, a transition-state analog of the intermediate in the ADA reaction, is a potent inhibitor of ADA. Its effects mimic the phenotype of genetic ADA deficiency, which is associated with severe immunodeficiency affecting both T- and B-cell functions. Inhibition of ADA by pentostatin leads to accumulation of intracellular adenosine and deoxyadenosine nucleotides, which can block DNA synthesis by inhibiting ribonucleotide reductase. Deoxyadenosine also inactivates S-adenosyl homocysteine hydrolase. The resulting accumulation of S-adenosyl homocysteine is particularly toxic to lymphocytes. Pentostatin also can inhibit RNA synthesis, and its triphosphate derivative is incorporated into DNA, resulting in strand breakage. In combination with 2'-deoxyadenosine, it is capable of inducing apoptosis in human monocytoid leukemia cells. Although the precise mechanism of cytotoxicity is not known, it is probable that the imbalance in purine nucleotide pools accounts for its antineoplastic effect in hairy cell leukemia and T-cell lymphomas.

Pentostatin is administered intravenously, and a single dose of 4 mg/m2 has a terminal t1/2 of 5.7 hours. The drug is eliminated almost entirely by renal excretion, and proportional reduction of dosage is recommended in patients with renal impairment.

Pentostatin (nipent) is available for intravenous use. The recommended dosage is 4 mg/m2 administered every other week. After hydration with 500—1000 mL of 5% dextrose in 0.45% saline, the drug is administered by rapid intravenous injection or by infusion during a period of up to 30 minutes, followed by an additional 500 mL of fluids. Extravasation does not produce tissue necrosis. Pentostatin is extremely effective in producing complete remissions in hairy cell leukemia. Complete responses of 58% and partial responses of 28% have been reported, even in patients who were refractory to interferon-a. Activity also is seen against CLL, CML, promyelocytic leukemia, cutaneous T-cell lymphoma, non-Hodgkin's lymphoma, and Langerhans cell histiocyto-sis. Pentostatin has no significant activity against solid tumors or MM.

Toxic manifestations include myelosuppression, GI symptoms, rashes, and abnormal liver function studies at standard (4 mg/m2) doses. Depletion of normal T cells occurs at these doses, and neutropenic fever and opportunistic infections can occur. immunosuppression may persist for several years after discontinuation of pentostatin therapy. At higher doses (10 mg/m2), major renal and neurological complications are encountered. The use of pentostatin in combination with fludarabine phosphate may result in severe or even fatal pulmonary toxicity.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook


Post a comment