title: 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.
abstract: 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.
authors.affiliation: Internal Medicine Department, University Hospital, Merkur, Zagreb, Croatia.
authors.forename: B
authors.initials: B
authors.lastname: Jaksic
authors.forename: M
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: I
authors.initials: I
authors.lastname: Krc
authors.forename: H
authors.initials: H
authors.lastname: Losonczi
authors.forename: J
authors.initials: J
authors.lastname: Holowiecki
authors.forename: A
authors.initials: A
authors.lastname: Planinc-Peraica
authors.forename: R
authors.initials: R
authors.lastname: Kusec
authors.forename: F
authors.initials: F
authors.lastname: Morabito
authors.forename: P
authors.initials: P
authors.lastname: Iacopino
authors.forename: D
authors.initials: D
authors.lastname: Lutz
mesh_terms: 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
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone