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Purine analoguesIn useNatural productNeeds review

Pentostatin

Also known as 2'-deoxycoformycin, deoxycoformycin, Nipent

An inhibitor of adenosine deaminase isolated from fermentation cultures of Streptomyces antibioticus. Its US label lists single-agent treatment of hairy cell leukaemia, in untreated and interferon-refractory patients with active disease.

From discovery to approval

  1. c. 1974 · Earliest report found

    The US label and a 1996 review say pentostatin is a fermentation product of Streptomyces antibioticus. The earliest report found under its chemical name is a 1974 chemistry paper by Woo and colleagues, 'A novel adenosine and ara-A deaminase inhibitor' (title only).[2][3][4][1]

  2. 1991-10-11 · FDA regular · 17 years after first description

    Nipent (pentostatin for injection), NDA 020122, original approval, classed as a new molecular entity with priority review and orphan status in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated here. The type regular is an inference: no accelerated-approval wording was found. The 2026 label lists single-agent treatment of untreated and alpha-interferon-refractory hairy cell leukaemia with active disease.[5]

How it works

A potent transition-state inhibitor of adenosine deaminase. The label says the resulting cytotoxicity is believed to come from raised intracellular dATP, which can block DNA synthesis, and that the precise antitumour mechanism in hairy cell leukaemia is not known.[1]

Where it came from and why

A 1996 review says that because children with congenital adenosine deaminase deficiency have lymphoid atrophy and severe immunodeficiency, it was hypothesised that pentostatin would be lymphocytotoxic, which proved true, prompting study in lymphoid neoplasms.

Cancers

  • Hairy cell leukaemia

    In an Eastern Cooperative Oncology Group study of 37 patients, the response rate among 27 who met all entry criteria was 96%, with 16 (59%) in complete and 10 (37%) in partial remission.[6]

  • Advanced lymphoid malignancy, including chronic lymphocytic leukaemia

    A trial of low-dose deoxycoformycin in 28 patients with advanced lymphoid malignancy found objective responses in 5.[7]

Worth knowing

  • A 1984 report describes two men with previously untreated hairy-cell leukaemia who achieved complete remission with low-dose intermittent pentostatin, with no myelosuppression, and a third patient who had just begun treatment.[8]
  • In an intergroup randomised comparison in untreated hairy cell leukaemia, confirmed complete remission was 76% (117 of 154) with pentostatin and 11% (17 of 159) with interferon alfa-2a, and relapse-free survival was longer with pentostatin.[9]
  • A 1996 review says pentostatin was expected to be most active in neoplasms with high adenosine deaminase, such as T-cell acute lymphoblastic leukaemia, but proved exceptionally active in hairy cell leukaemia, a B-cell neoplasm with low enzyme levels.[3]
  • The Drugs@FDA history lists the original application (NDA 020122) as approved on 11 October 1991, a new molecular entity with priority review and orphan status.[5]

References

  1. Hospira, Inc. Nipent (pentostatin): prescribing information. DailyMed, set ID 674e0e6d-46ed-4868-9196-04019d667716, published 3 July 2026. Read 26 October 2026. Source
  2. Woo PWK, Dion HW, Lange SM, Dahl LF, Durham LJ. A novel adenosine and ara-A deaminase inhibitor, (R)-3-(2-deoxy-β-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol. Journal of Heterocyclic Chemistry. 1974;11(4):641-3. DOI
  3. Spiers AS. Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases. Haematologia (Budap). 1996;27(2):55-84. PubMed
  4. Showalter HD, Bunge RH, French JC, Hurley TR, Leeds RL, Leja B, et al. Improved production of pentostatin and identification of fermentation cometabolites. J Antibiot (Tokyo). 1992;45(12):1914-8. PubMedDOI
  5. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020122 (pentostatin; Nipent). Page read 2026-10-26. Source
  6. Spiers AS, Moore D, Cassileth PA, Harrington DP, Cummings FJ, Neiman RS, et al. Remissions in hairy-cell leukemia with pentostatin (2'-deoxycoformycin). N Engl J Med. 1987;316(14):825-30. PubMedDOI
  7. Grever MR, Leiby JM, Kraut EH, Wilson HE, Neidhart JA, Wall RL, et al. Low-dose deoxycoformycin in lymphoid malignancy. J Clin Oncol. 1985;3(9):1196-201. PubMedDOI
  8. Spiers AS, Parekh SJ, Bishop MB. Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin). J Clin Oncol. 1984;2(12):1336-42. PubMedDOI
  9. Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, et al. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol. 1995;13(4):974-82. PubMedDOI