Pentostatin (Nipent) is a nucleoside analog
that inhibits the activity of the enzyme adenosine deaminase.
Inhibition of adenosine deaminase blocks the deamination of adenosine
to inosine and deoxyadenosine to deoxyinosine in the purine salvage
pathway. This accumulation of metabolites inhibits ribonucleotide
reductase, which depletes the nucleotide pool and limits DNA
synthesis. Adenosine deaminase is concentrated in lymphoid tissue,
including both T and B lymphocytes. It appears that the cytotoxic
effect of pentostatin is independent of intracellular concentrations
of adenosine deaminase.
The 1990s marked a resurgence of interest in pentostatin, a drug that
was first administered to patients with acute leukemia in the 1970s.
In clinical trials, pentostatin has demonstrated response rates of
25% to 30% in heavily pretreated patients with chronic lymphocytic
leukemia (CLL) and response rates of 10% to 20% in heavily pretreated
patients with indolent lymphoma. Typical toxicities that occur with
the use of pentostatin are cytopenias and infections.
Because patients with lymphoproliferative disorders already have an
underlying immunodeficiency disorder, pentostatin causes additional
depression of both T and B lymphocytes, and can make these patients
more susceptible to certain opportunistic and viral infections, such
as Candida, Aspergillus, Pneumocystis, and
herpesvirus infections. To prevent these complications, patients with
non-Hodgkins lymphoma (NHL) who are treated with pentostatin
should be placed on prophylactic antibiotics, such as
trimethoprim-sulfamethoxazole and acyclovir (Zovirax). Additionally,
patients should be closely monitored for these and other infections,
and should receive aggressive treatment if infection is suspected.
New Applications for Pentostatin
At a meeting in July 1999, clinical and laboratory investigators from
the United States and Europe gathered to discuss new applications for
pentostatin alone and in various combinations for patients with
indolent NHLs. The promising data presented at this meeting form the
basis for this supplement.
Dr. Fernando Cabanillas reviews the role of pentostatin and other
purine nucleoside analogs in the management of indolent NHL. Dr. Nam
Dang and colleagues discuss a phase II trial evaluating the role of
pentostatin in relapsed/refractory T-cell lymphomas in relation to
CD26 expression, which is integral to adenosine deaminase cell
surface expression and function. A planned trial evaluating the use
of pentostatin in combination with rituximab (Rituxan) in patients
with B-cell malignancies is described by
Dr. Robert Drapkin. The use of pentostatin in combination with
alkylating agents, interferon, and cordycepin is reviewed by Dr.
Francine Foss. Dr. Claire Dearden concludes the supplement by
describing the activity of pentostatin in primary cutaneous T-cell
Future studies should explore the benefit of lower-dose regimens of
pentostatin to reduce toxicity, and should continue to explore the
potential synergy between pentostatin and other T-celltargeted