Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.
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PMID:Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. 206 53

Pentostatin (2'-deoxycoformycin, DCF) was administered to 17 patients with a variety of lymphoid neoplasms, both T- and B-cell, that were refractory to conventional treatments. Several responses and 2 complete remissions occurred. Toxic effects were less severe than previously described: this may be attributable to relatively low doses of DCF or to precautions taken to prevent tumour lysis syndrome. DCF appears valuable as a second-line treatment in non-Hodgkin's lymphomas and as initial treatment in T-cell chronic lymphocytic leukaemia and mycosis fungoides. Although myelosuppression is mild, immunosuppression and superinfection are potential hazards of treatment with DCF. The ocular toxicity of DCF, previously described as conjunctivitis, appears to be a keratitis of moderate severity which requires further study.
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PMID:Effectiveness of pentostatin (2'-deoxycoformycin) in refractory lymphoid neoplasms. 660 39

Thirty-seven eligible patients with advanced non-Hodgkin's lymphoma of low-grade, T-cell intermediate- and high-grade histology were treated with pentostatin (2'-deoxycoformycin, dCF) 4mg/m2 i.v. weekly for 3 weeks and then every 14 days to be followed after 3 doses by the same dosage every 4 weeks until maximum response or progression. Only patients with no more than two chemotherapy regimens were entered in this trial. All patients had measurable disease, performance status of 1,0 and 2 and adequate bone marrow, renal and liver function. Five of 37 eligible patients experienced a partial response of 8 months' median duration (range 7-12). The response rate was 17% in low-grade, 8% in T-cell intermediate- and high-grade and 14% in cutaneous T cell lymphoma. The only eligible patient with Hodgkin's disease underwent progression while on treatment. One case presented with grade 3 leukopenia and another one died of septicaemia, possibly treatment-related. Elevated but reversible creatinine levels were observed in 13% of patients and conjunctivitis in 7%. The toxicity of dCF at this low-dose schedule was acceptable, but the therapeutic activity in pretreated patients with low-grade, T-cell intermediate- and high-grade and cutaneous T-cell lymphomas was limited.
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PMID:Pentostatin (2'-deoxycoformycin, dCF) in patients with low-grade (B-T-cell) and intermediate- and high-grade (T-cell) malignant lymphomas: phase II study of the EORTC Early Clinical Trials Group. 860 44

Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in 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 speculated that pentostatin would be lymphocytotoxic, and this proved to be the case, promoting 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 its T cell variety. Although pentostatin proved to be active in ALL, large doses were required and toxic effects outweighted 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, immunosuppression, 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 immunosuppresive 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.
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PMID:Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role In Cancer Chemotherapy, and Future Prospects. 1184 52

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.
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PMID:Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases. 1465 Dec 24

Pentostatin has been shown to be active in a variety of B- and T-cell malignancies. The drug is a tight inhibitor of adenosine deaminase, a key degradative enzyme of purine metabolism present in all human tissues, with the highest levels found in the lymphoid system. Early clinical trials indicated that this agent was highly active in acute lymphoblastic leukemias with high intracellular adenosine deaminase levels. Relatively high doses of the drug were needed, which was associated with severe adverse events. Through the efforts of a few investigators, better tolerated, low-dose regimens have been shown to be extremely active in lymphoproliferative diseases with very low intracellular adenosine deaminase levels such as hairy cell leukemia, B- and T-cell chronic leukemias, T-cell cutaneous lymphomas and low-grade non-Hodgkin lymphomas. Clinical as well as experimental data have indicated that this drug induces lymphocyte-specific cytotoxicity, and myelosuppressive adverse events have been minimal. Although all the purine analogs have shown similar activity, the advantage of pentostatin is the relatively specific cytotoxicity against lymphocytes, which permits treatment even in patients with severe cytopenias. Although no direct comparisons of the purine analogs have been performed, pentostatin may be preferred due to this property.
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PMID:Pentostatin and purine analogs for indolent lymphoid malignancies. 1656 86