Theophylline, pentostatin (Nipent), and chlorambucil: a dose-escalation study targeting intrinsic biologic resistance mechanisms in patients with relapsed lymphoproliferative disorders.

Abstract:

:In spite of the chemosensitivity seen with the initial treatment of malignant lymphoid disorders, relapse is common and death most often occurs as a result of disease progression. This is related to a multitude of resistance mechanisms associated with the various lymphoproliferative disorders. As a result, therapies targeting intrinsic drug-resistance mechanisms are evolving and have become an active area of research. In vitro studies of human chronic lymphocytic leukemia cells incubated with theophylline, a phosphodiesterase inhibitor, resulted in downregulation of bcl-2 concomitant with induction of apoptosis. We describe the preclinical basis for a novel combination therapy involving pentostatin (Nipent; SuperGen, San Ramon, CA), chlorambucil, and theophylline in the treatment of patients with relapsed chronic lymphoproliferative disorders. An ongoing study based on such justification, which is currently accruing patients, is also described. Results from this trial appear promising, and a phase II study is now being planned.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Byrd JC,Grever MR,Waselenko JK,Willis CR,Park K,Goodrich A,Lucas MA,Shinn C,Flinn IW

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

37-40

issue

2 Suppl 5

eissn

0093-7754

issn

1532-8708

journal_volume

27

pub_type

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