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 5 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 3 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^-6 M) and in urine (10^-3 M). 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 5 other patients. No responses were observed in 6 patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.