title: Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia.
abstract: OBJECTIVE
  The addition of monoclonal antibodies to chemotherapy has significantly improved treatment of chronic lymphocytic leukemia (CLL). Based on excellent results with the chemotherapy-only regimen fludarabine, cyclophosphamide, and mitoxantrone (FCM), we built a new chemoimmunotherapy combination--rituximab plus FCM (R-FCM). We report a phase II clinical trial consisting of an initial treatment with R-FCM followed by rituximab maintenance.
  
  
  METHODS
  Seventy-two untreated CLL patients age 70 years or younger received rituximab 500 mg/m(2) on day 1 (375 mg/m(2) the first cycle), fludarabine 25 mg/m(2) IV on days 1 to 3, cyclophosphamide 200 mg/m(2) on days 1 to 3, and mitoxantrone 6 mg/m(2) IV on day 1, given at 4-week intervals with up to six cycles supported with colony-stimulating factor. Patients achieving response received maintenance with rituximab 375 mg/m(2) every 3 months for 2 years.
  
  
  RESULTS
  The overall response, minimal residual disease (MRD) -negative complete response (CR), MRD-positive CR, and partial response rates were 93%, 46%, 36%, and 11%, respectively. Severe neutropenia developed in 13% of patients. Major and minor infections were reported in 8% and 5% of cycles, respectively. Advanced clinical stage, del(17p), or increased serum beta2-microglobulin levels correlated with a lower CR rate.
  
  
  CONCLUSIONS
  R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Parameters correlating with a lower response rate were advanced clinical stage, high serum beta2-microglobulin levels, and del(17p). Based on these results, R-FCM warrants further investigation in randomized clinical trials.
authors.affiliation: Department of Hematology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. fbosch@clinic.ub.es
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Pau
authors.initials: P
authors.lastname: Abrisqueta
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: María José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.forename: Christelle
authors.initials: C
authors.lastname: Ferra
authors.forename: Marcos
authors.initials: M
authors.lastname: González Diaz
authors.forename: Eugenia
authors.initials: E
authors.lastname: Abella
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: Félix
authors.initials: F
authors.lastname: Carbonell
authors.forename: José Antonio
authors.initials: JA
authors.lastname: García Marco
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.forename: Secundino
authors.initials: S
authors.lastname: Ferrer
authors.forename: Encarnación
authors.initials: E
authors.lastname: Monzó
authors.forename: Yolanda
authors.initials: Y
authors.lastname: González
authors.forename: Cristina
authors.initials: C
authors.lastname: Estany
authors.forename: Isidro
authors.initials: I
authors.lastname: Jarque
authors.forename: Olga
authors.initials: O
authors.lastname: Salamero
authors.forename: Ana
authors.initials: A
authors.lastname: Muntañola
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine