Deoxycoformycin in therapy of refractory lymphoid neoplasms.
Knowledge of the vital role of the purine degradative enzyme adenosine deaminase (ADA) in the differentiation of T and B lymphocytes has stimulated interest in the pharmacologic inhibition of ADA as specific cytotoxic therapy for lymphoproliferative diseases. 2'-Deoxycoformycin (DCF) is a tight-binding ADA-inhibitor and has shown activity in T and B cell neoplasms. In this phase-II study, the efficacy and toxicity of DCF in chronic T and B cell neoplasms is investigated. We report the preliminary results of treatment in 27 patients (8 with Sézary syndrome, 11 with B-chronic lymphocytic leukemia (CLL), and 8 with hairy cell leukemia (HCL)), who were refractory to conventional therapy. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Three of the 8 patients with Sézary syndrome and 3 of the 11 patients with B-CLL attained a partial remission. One complete and 7 partial remissions have been achieved thus far in the 8 patients with HCL refractory to interferon alpha treatment. Other than nausea in 10 patients (mainly grade 1 and 2), transient skin rash in 4 patients and Herpes infections in 4 patients (mainly grade 2), no other major toxicities were observed. Thus DCF is highly active in hairy cell leukemia that did not respond to interferon alpha, and shows moderate activity in refractory Sézary syndrome and B-CLL.
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AD
Medizinische Universitäts-Poliklinik, Heidelberg, FRG.
Thaler
J
J
Kuse
R
R
Willemze
R
R
Mandelli
F
F
Lauria
F
F
Zittoun
R
R
Stryckmans
P
P
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004341:Drug Evaluation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy*; D015649:Pentostatin; D012263:Ribonucleosides / Q000627:therapeutic use*; D012751:Sezary Syndrome / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy; D013601:T-Lymphocytes / Q000187:drug effects
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin