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Leukemia & Lymphoma Sep 2000Although 2'-deoxycoformycin (dCF) has been reported in clinical trials to be less effective against myeloid than lymphoid malignancies, it may be useful for treating... (Review)
Review
Although 2'-deoxycoformycin (dCF) has been reported in clinical trials to be less effective against myeloid than lymphoid malignancies, it may be useful for treating monocytic leukemia with the aid of 2'-deoxyadenosine (dAd) analogs. In the presence of 10 microM dAd, the concentration of dCF required to inhibit the viability of monocytoid leukemia cells was much lower than that required on normal or non-monocytoid malignant cells in primary culture. Among the dAd analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in combination with dCF. Although dCF alone slightly but significantly prolonged the survival of mice inoculated with U937 monocytic leukemia cells, combined treatment with dCF and AraA markedly prolonged the survival. These results suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia.
Topics: Animals; Antibiotics, Antineoplastic; Antimetabolites; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Dose-Response Relationship, Drug; Humans; Leukemia, Monocytic, Acute; Pentostatin; Vidarabine
PubMed: 10975384
DOI: 10.3109/10428190009053539 -
Haematologia 1996Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of... (Review)
Review
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.
Topics: Adenosine Deaminase Inhibitors; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Synergism; Enzyme Inhibitors; Forecasting; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Kidney Diseases; Mice; Molecular Structure; Neoplasm Proteins; Nervous System Diseases; Pentostatin; Vidarabine
PubMed: 14651224
DOI: No ID Found -
Experimental Parasitology Apr 2019The aim of this study was to evaluate in vitro the efficacy of cordycepin and pentostatin (alone or combined) against Trypanosoma cruzi, as well as the therapeutic...
The aim of this study was to evaluate in vitro the efficacy of cordycepin and pentostatin (alone or combined) against Trypanosoma cruzi, as well as the therapeutic efficiency of protocols of cordycepin and pentostatin combinations in mice experimentally infected with T. cruzi. In vitro, the cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) exerted potent trypanocidal effect against T. cruzi (Colombian strain), similarly to benznidazole, which is the reference drug. For epimastigotes, the lethal dose of cordycepin capable of killing 50% (LD) and 20% (LD) of the parasites was 0.072 and 0.031 mg/mL, respectively and for trypomastigotes was 0.047 and 0.015 mg/mL, respectively. The combined use of cordycepin and pentostatin resulted in a LD and LD for epimastigotes of 0.068 and 0.027 mg/mL, respectively, as well as 0.056 and 0.018 mg/mL for trypomastigotes, respectively. In vivo, the combined use of cordycepin and pentostatin did not show the expected curative effect, however it was able to control the parasitema in the peak period. In summary, the combination of cordycepin and pentostatin showed no curative effect in mice infected by T. cruzi, despite the in vitro reduction of epimastigotes and trypomastigotes.
Topics: Analysis of Variance; Animals; Antiprotozoal Agents; Chagas Disease; Deoxyadenosines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heart; Lethal Dose 50; Mice; Myocardium; Neglected Diseases; Nifurtimox; Nitroimidazoles; Nonlinear Dynamics; Parasitemia; Pentostatin; Random Allocation; Regression Analysis; Trypanosoma cruzi
PubMed: 30825499
DOI: 10.1016/j.exppara.2019.02.016 -
Oncology (Williston Park, N.Y.) Jun 1988Promising results in the treatment of indolent lymphomas have been reported with the use of 2'deoxycoformycin. This antimetabolite, an adenosine deaminase inhibitor,... (Review)
Review
Promising results in the treatment of indolent lymphomas have been reported with the use of 2'deoxycoformycin. This antimetabolite, an adenosine deaminase inhibitor, also shows particular efficacy in hairy cell leukemia. Of 65 patients treated to date, 44 have achieved complete and lasting remission after a limited course of deoxycoformycin. While results are not as striking as those in hairy cell leukemia, deoxycoformycin may also be a valuable adjunct to alkylating agents in the treatment of CLL. The drug also is being studied in the treatment of mycosis fungoides and other lymphoid neoplasms. Side effects in all neoplasms are dose- and schedule-dependent.
Topics: Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Mycosis Fungoides; Pentostatin
PubMed: 3079330
DOI: No ID Found -
Hematology and Cell Therapy Dec 19962'-deoxycoformycin (DCF) is the oldest of the nucleoside analogs in clinical practice. The main use has been in the B and T lymphoproliferative disorders. The early... (Review)
Review
2'-deoxycoformycin (DCF) is the oldest of the nucleoside analogs in clinical practice. The main use has been in the B and T lymphoproliferative disorders. The early significant activity with a high remission rate reported in hairy cell leukemia (HCL) has been confirmed within our group. Data from a large phase II study, which comprised 165 evaluable patients with HCL treated with DCF 4mg/m2 every 2 weeks until maximal response collected over a ten-year period, shows a very long disease-free interval with 76% of the complete responders still in remission at 6 years. Some activity has been reported in chronic lymphocytic leukemia and an outline of a phase II study with low dose DCF given over five days every month is summarised. DCF has been shown to be active in mature T-cell malignancies, chiefly T-prolymphocytic leukemia (T-PLL) and the cutaneous T-cell lymphoma, Sezary syndrome. Its efficacy in other forms of T-cell lymphoma has been less consistent but, bearing in mind the poor outlook of these disorders, the data suggest that DCF should be considered as part of the treatment strategy. In T-PLL, for example, partial remitters (and non-responders) to DCF have received the monoclonal antibody CAMPATH-1H with excellent results.
Topics: Antibiotics, Antineoplastic; Clinical Trials, Phase II as Topic; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Pentostatin; Sezary Syndrome
PubMed: 9137963
DOI: No ID Found -
The Journal of the Royal College of... Sep 2011Posterior reversible encephalopathy syndrome (PRES) is a combined clinical and radiological syndrome characterised by headaches, encephalopathy, seizures and visual... (Review)
Review
Posterior reversible encephalopathy syndrome (PRES) is a combined clinical and radiological syndrome characterised by headaches, encephalopathy, seizures and visual loss. We present the case of a 55-year-old male who developed this condition following treatment with deoxycoformycin and alemtuzumab. We review the literature considering diagnosis, pathophysiology and optimal strategies for treatment of this condition.
Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Pentostatin; Posterior Leukoencephalopathy Syndrome
PubMed: 21949916
DOI: 10.4997/JRCPE.2011.306 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Dec 2021Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors.... (Review)
Review
Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. However, the high cost hampers its application. In the past 10 years, the biosynthesis of pentostatin were focused on strain breeding, optimization of medium composition and fermentation process. To date, there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin. This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.
Topics: Anti-Bacterial Agents; Pentostatin
PubMed: 34984865
DOI: 10.13345/j.cjb.210066 -
Cancer Clinical Trials 19812'-deoxycoformycin (2'-dCF) is a powerful inhibitor of adenosine deaminase (ADA), an enzyme found in high concentrations in lymphoid tissue. Although inactive in... (Review)
Review
2'-deoxycoformycin (2'-dCF) is a powerful inhibitor of adenosine deaminase (ADA), an enzyme found in high concentrations in lymphoid tissue. Although inactive in preclinical tumor models, 2'-dCF has shown clinical antitumor activity as a single agent in lymphoid malignancies. This drug has the added potential of being useful as a potentiator of other antitumor agents which are deactivated by ADA. It is also possible that the drug has potential as an immunosuppressive agent. Phase I studies are ongoing and phase II trials are planned to define the antitumor spectrum of this agent.
Topics: Animals; Antineoplastic Agents; Coformycin; Humans; Kinetics; Neoplasms, Experimental; Pentostatin; Ribonucleosides
PubMed: 7018725
DOI: No ID Found -
Leukemia & Lymphoma Jun 2002Purine analogs are effective in the treatment of several chronic lymphoproliferative disorders (CLPD) including hairy cell leukemia (HCL). To date, little evidence... (Review)
Review
Purine analogs are effective in the treatment of several chronic lymphoproliferative disorders (CLPD) including hairy cell leukemia (HCL). To date, little evidence exists that these drugs are oncogenic. We report a case of HCL in a 66-year-old male treated with 2-deoxycoformycin. Just over 1 year following completion of his treatment, falling platelet and white cell counts were associated with the development of dysplastic features in his bone marrow and a rising blast cell count, culminating in the development of acute myeloid leukemia (AML). To the best of our knowledge only two previous cases of AML have been linked to treatment of HCL with purine analogs, both with 2-chlorodeoxyadenosine. We emphasize the need for long term follow up of patients treated with purine analogs and suggest that even those who are apparently cured be monitored periodically.
Topics: Acute Disease; Aged; Antimetabolites, Antineoplastic; Fatal Outcome; Humans; Leukemia, Hairy Cell; Leukemia, Myeloid; Leukocyte Count; Male; Myelodysplastic Syndromes; Neoplasms, Second Primary; Pentostatin; Platelet Count
PubMed: 12153007
DOI: 10.1080/10428190290021416 -
Cancer Chemotherapy and Pharmacology 1981Deoxycoformycin (DCF) is a tight-binding inhibitor of adenosine deaminase (ADA) currently undergoing phase I--II evaluation. Neurological toxicity has been a frequent...
Deoxycoformycin (DCF) is a tight-binding inhibitor of adenosine deaminase (ADA) currently undergoing phase I--II evaluation. Neurological toxicity has been a frequent and occasionally severe complication of treatment with this drug. A T-cell leukemia patient with an Ommaya reservoir was treated with DCF, and the pharmacokinetics of the drug in the cerebrospinal fluid and plasma were studied. DCF penetrates the cerebrospinal fluid and achieves levels as high as 1/10 the concurrent plasma levels. The accumulation of adenosine and deoxyadenosine in plasma, cerebrospinal fluid, and urine was monitored; the neuropharmacological effect of these metabolites is discussed.
Topics: Adenosine; Adult; Coformycin; Deoxyadenosines; Electroencephalography; Humans; Male; Nervous System Diseases; Pentostatin; Ribonucleosides
PubMed: 6975188
DOI: 10.1007/BF00258479