Clinical Pharmacology of Deoxycoformycin

Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/d...

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Bibliographic Details
Published in:Blood 1981-07, Vol.58 (1), p.91-96
Main Authors: Major, P.P., Agarwal, R.P., Kufe, D.W.
Format: Article
Language:English
Subjects:
Adenosine - blood
Adenosine Deaminase Inhibitors
Adenosine Kinase - blood
Adolescent
Adult
Aged
Bronchitis - chemically induced
Coformycin - analogs & derivatives
Coformycin - therapeutic use
Coformycin - toxicity
Coma - chemically induced
Conjunctivitis - chemically induced
Deoxyadenosines - blood
Female
Humans
Kidney Diseases - chemically induced
Leukemia, Lymphoid - drug therapy
Lymphoma - drug therapy
Male
Middle Aged
Mycosis Fungoides - drug therapy
Nucleoside Deaminases - antagonists & inhibitors
Pentostatin
Phosphotransferases (Alcohol Group Acceptor)
Phosphotransferases - blood
Ribonucleosides - therapeutic use
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Summary:Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10–6M) and in urine (10–3M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V58.1.91.91