CLINICAL-PHARMACOLOGY OF DEOXYCOFORMYCIN

Abstract

Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA; EC 3.5.4.4). Courses (21) of DCF were administered to 13 patients 15-78 yr old. Eight patients had T-cell disorders and 5 patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5-30 mg/m2 per day, and the duration of the courses ranged from 1-5 days. The DCF plasma half-life ranged from 4.9-6.2 h and was independent of dose. The dose-limiting toxicities involved the CNS and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias and myalgias. Mortality was encountered in 3 patients. The toxic effects may be 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: 1 in a patient with T-cell ALL [acute lymphoblastic leukemia] and another in a patient with mycosis fungoides. Minimal responses characterized by declines in peripheral blast counts or partial resolution of adenopathy were observed in 5 other patients. No responses were observed in 6 patients. DCF is effective in the treatment of T-cell lymphoid malignancies.