Treatment of cutaneous T cell lymphoma with 2'-deoxycoformycin (pentostatin).
2'-Deoxycoformycin, a potent inhibitor of adenosine deaminase, was administered to three patients with cutaneous T cell lymphoma refractory to multiple treatment modalities. Patient 1, who received 5 mg/m2/day for 3 days at 35- to 71-day intervals, has achieved a complete remission greater than 16 months in duration. Patient 2 had progressive disease despite two courses of 2'-deoxycoformycin at a dose of 5 mg/m2/day for 3 days at 28-day intervals. The third patient, who was treated with 4 mg/m2 2'-deoxycoformycin weekly to biweekly, had an initial response, but the disease progressed after eight treatments. Only one patient had any side effects: Patient 1 developed reversible episcleritis, mild elevation of liver enzymes, and persistent nausea and vomiting. In red blood cells of all patients, there was near complete inhibition of adenosine deaminase (91% to 96%) and S-adenosylhomocysteine hydrolase (89% to 95%) activities with treatment. In peripheral blood lymphocytes, adenosine deaminase was inhibited by 85% to 98% and S-adenosylhomocysteine hydrolase by 51% to 88%. The deoxyadenosine triphosphate level, reflected by the total cellular adenine deoxyribonucleotide measurement in erythrocytes, was noted to be modestly elevated during treatment, with the highest level in the patient who demonstrated the only complete response and the only toxic effects. Low-dose 2'-deoxycoformycin appears to be safe but may be an insufficiently intensive regimen to treat refractory cutaneous T cell lymphoma. With proper biochemical monitoring, higher doses may be both safe and more effective.
Dang-Vu
A P
AP
Division of Dermatology, Duke University Medical Center, Durham, NC 27710.
Olsen
E A
EA
Vollmer
R T
RT
Greenberg
M L
ML
Hershfield
M S
MS
D000243:Adenosine Deaminase / Q000097:blood; D058892:Adenosine Deaminase Inhibitors; D043383:Adenosylhomocysteinase; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003070:Coformycin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D006867:Hydrolases / Q000097:blood; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015649:Pentostatin; D012263:Ribonucleosides / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000201:enzymology
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000243:Adenosine Deaminase