High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna.
BACKGROUND
In recent years, much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced, progressive B-cell chronic lymphocytic leukemia (CLL) patients. For this reason, the International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia Cooperative Group, has begun a randomized multicenter trial comparing Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with continuous high dose chlorambucil (HD-CLB).


METHODS
During the period January 1987 to May 1993, 228 previously untreated CLL patients from 7 cooperative institutions were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (> 9), and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The response to therapy was defined by reduction of the initial TTM score. The end points of the trial were response rate, survival, and toxicity.


RESULTS
HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response+partial response) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 68 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms.


CONCLUSIONS
The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients with advanced and/or progressive CLL. Therefore, the authors recommend its wider use, possibly in comparison with and/ or in combination with new therapeutic agents, such as purine analogues.
Jaksic
B
B
Internal Medicine Department, University Hospital, Merkur, Zagreb, Croatia.
Brugiatelli
M
M
Krc
I
I
Losonczi
H
H
Holowiecki
J
J
Planinc-Peraica
A
A
Kusec
R
R
Morabito
F
F
Iacopino
P
P
Lutz
D
D
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D002699:Chlorambucil / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone