DRUG STUDY AND INFORMATION FORM Generic Name: Pentostatin (2-Deoxycoformycin) Trade Name: Nipent, Deoxycoformycin Drug Class:

Purine Analogs Structure/Chemistry: Transition state analog of the intermediate in the adenosine deaminase reaction

Pharmacodynamics

Mechanism of Action: Inhibits adenosine deaminase (ADA) which leads to the accumulation of adenosine and deoxyadenosine nucleotides. This accumulation blocks DNA synthesis by inhibiting RNR (ribonucleotide reductase). Deoxyadenosine also activates S-adenosyl homocysteine hydrolase; accumulation of S-adenosyl homocysteine is particularly toxic to lymphocytes. Pentostatin also inhibits RNA synthesis and its triphosphate derivative is incorporated into DNA, resulting in strand breakage.

Pharmacologic Effects: Imbalance of purine nucleotide pools may account for cytotoxicity as well as genomic damage and RNA synthesis inhibition.

Drug Resistance or Tolerance:

Pharmacokinetics

Absorption: Given IV in single doses of 4 mg/m2 given once every other week. Fluids are administered before and after drug infusion.

Distribution:

Elimination: t1/2 of 5.7 hours. Eliminated almost entirely by renal excretion (adjust dosage for renal dysfunction)

Metabolism:

Adverse Side Effects/Toxicity: Myelosuppression (may last for years after therapy discontinuation), GI symptoms, skin rashes, and abnormal liver function studies. Depletion of T cells occurs leading to neutropenic fever and opportunistic infections. High doses of pentostatin may lead to major renal and neurological complications.

Drug Interactions: Pentostatin given in combination with fludarabine phosphate may result in severe or fatal pulmonary toxicity.

Therapeutic uses: Produces complete remissions (58%) and partial responses (28%) in hairy cell leukemia. Cladribine is used preferentially for the treatment of hairy cell leukemia instead.

Miscellaneous: Originally isolated from Streptomyces antiobioticus