2-Chlorodeoxyadenosine treatment of low-grade lymphomas.
OBJECTIVE
Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas.


METHODS
Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies).


RESULTS
An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia.


CONCLUSIONS
This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.
Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
A C
AC
Kay
A
A
Saven
C J
CJ
Carrera
D A
DA
Carson
D
D
Thurston
E
E
Beutler
L D
LD
Piro
D015762:2-Chloroadenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000209:etiology; D001855:Bone Marrow Diseases / Q000139:chemically induced; D017338:Cladribine; D003839:Deoxyadenosines / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008224:Lymphoma, Follicular / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D015762:2-Chloroadenosine; D017338:Cladribine