2-chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III-IV non-Hodgkin's lymphoma.
OBJECTIVE
This phase II multi-institutional trial was designed to assess response and toxicity of 2-chlorodeoxyadenosine (2-CDA) in patients with previously untreated follicular lymphoma. The clinical significance of detecting cells carrying the t(14;18) translocation (bcl-2/JH rearrangement) in peripheral blood and bone marrow by polymerase chain reaction (PCR) before, during and after treatment was also examined.


METHODS
Between May 1993 and October 1995, 37 patients were accrued: male/female: 15/22, median age 51 years (range: 20-78), stage III/IV: 9/28. Patients received a total 2-CDA dose of 0.7 mg/kg as continuous s.c. or i.v. infusions over 7 days, every 28 days for a maximum of 5 cycles. A total of 165 cycles were administered. In 25 patients, blood and bone marrow before, during and after treatment were available for PCR analysis of the bcl-2/JH rearrangements.


RESULTS
All 37 patients were evaluable for response and toxicity. The overall response rate was 84% (95% confidence interval, 68%-94%) with 14% CR (n = 5) and 70% PR (n = 26) and a median time to treatment failure of 15.7 months. bcl-2/JH rearrangement in peripheral blood and/or bone marrow was found in 10/25 of patients (40%) before treatment and 5 of these became repeatedly negative after 2-CDA therapy. There was no apparent association between bcl-2/ JH result and response. In 11 patients, 2-CDA was stopped because of progressive disease (n = 4), myelotoxicity (grade 2-3, n = 4), and other causes (n = 3, pulmonary embolism, metabolic disorder, and patient's decision). Four patients (11%) suffered from infections (grade 2-3). In 6 patients, persistent thrombocytopenia of 7.5 months (range: 3-21) occurred after completion of the 5 cycles.


CONCLUSIONS
2-CDA is active in untreated follicular lymphomas, but time to treatment failure suggests no advantage compared with standard treatment and toxicity on haematopoietic stem cells appears to be more pronounced. Molecular remission is induced in a considerable proportion of patients with disappearance of the bcl-2/JH rearrangement, and its possible significance as a predictive factor for quality of response and relapse warrants further study.
Betticher
D C
DC
Institute of Medical Oncology, Inselspital, Berne, Switzerland.
Zucca
E
E
von Rohr
A
A
Egger
T
T
Radford
J A
JA
Ambrosetti
A
A
Bürki
K
K
Rufener
B
B
Schmitz
S F
SF
Cerny
T
T
D015762:2-Chloroadenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome
D003839:Deoxyadenosines; D015762:2-Chloroadenosine; C055994:2-chloro-3'-deoxyadenosine