Pentostatin (2'-deoxycoformycin, dCF) is a
purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of
adenosine deaminase (ADA), an
enzyme essential in the cellular metabolism of
purines. Children with congenital absence of ADA suffer from
atrophy of lymphoid tissues and
severe combined immune deficiency (SCID) syndrome. It was hypothesized that
pentostatin would be lymphocytotoxic and this proved to be true; this finding prompted its investigation in lymphoid
neoplasms. It was anticipated that
pentostatin would be most active in
neoplasms with high intracellular concentrations of ADA, e.g.
acute lymphocytic leukemia (ALL), particularly of the T-cell variety. Although
pentostatin proved to be active in ALL, large doses were required and major toxic effects outweighed therapeutic benefits. By contrast,
pentostatin proved to be exceptionally active in
hairy cell leukemia (HCL), a B-cell
neoplasm with low intracellular concentrations of ADA.
Pentostatin has since been shown to possess activity in
chronic lymphocytic leukemia,
prolymphocytic leukemia,
cutaneous T-cell lymphomas, adult
T-cell lymphoma-
leukemia, and low grade non-Hodgkin's
lymphomas. It potentiates the activity of
vidarabine against viruses and against the cells of
acute myeloid leukemia.
Pentostatin is inactive in
melanoma and
renal carcinoma, but has not been adequately evaluated in other solid
tumors. The toxic effects of
pentostatin include
renal failure, central nervous system (CNS) depression, immunosuppresion,
keratoconjunctivitis, and
opportunistic infections. In the absence of pre-existing bone marrow compromise,
pentostatin produces only mild myelosuppression. Aside from its use as an
antineoplastic agent,
pentostatin has potential applications as an immunosuppressive
drug, as an
antiviral agent, as an
antimalarial compound, and in the protection of cells of the CNS from damage induced by
ischemia and
anoxia. Clinical studies with
pentostatin are ongoing, and its roles in the management of neoplastic and non-neoplastic diseases have yet to be fully defined.