Low-dose deoxycoformycin in lymphoid malignancy.
Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.
Grever
M R
MR
Leiby
J M
JM
Kraut
E H
EH
Wilson
H E
HE
Neidhart
J A
JA
Wall
R L
RL
Balcerzak
S P
SP
D058892:Adenosine Deaminase Inhibitors; D001402:B-Lymphocytes / Q000201:enzymology; D002177:Candidiasis / Q000139:chemically induced; D003070:Coformycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D003231:Conjunctivitis / Q000139:chemically induced; D004334:Drug Administration Schedule; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006566:Herpesviridae Infections / Q000139:chemically induced; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000201:enzymology; D008111:Liver Function Tests; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology; D008875:Middle Aged; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D012141:Respiratory Tract Infections; D012263:Ribonucleosides / Q000008:administration & dosage*
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases