title: Phase I study of Rituximab-CHOP regimen in combination with granulocyte colony-stimulating factor in patients with follicular lymphoma.
abstract: OBJECTIVE
  Rituximab is an anti-CD20 monoclonal antibody, and it is used to treat B-cell lymphomas. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the mechanisms through which rituximab exerts its effects. Granulocyte colony-stimulating factor (G-CSF) enhances the cytotoxicity of neutrophils through ADCC, and it can be speculated that a combination of rituximab and G-CSF may augment the treatment efficacy of rituximab.
  
  
  METHODS
  We administered rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) treatment with G-CSF to 15 patients with follicular lymphoma, and we investigated the safety and efficacy of this regimen. We investigated ADCC activity in neutrophils and the expression of cell surface antigens including Fcgamma receptor type I [FcgammaRI (CD64)] on neutrophils to determine the optimal dose of G-CSF.
  
  
  RESULTS
  Adverse reactions occurred in 14 of 15 patients and consisted mainly of grade 3/4 hematological toxicity. The response rate was 100%, with complete remission in 12 patients (80%) and partial remission in 3 patients (20%). At 14 months, the median length of the observation period, 2 of 12 patients had relapsed. G-CSF administration increased both FcgammaRI expression and ADCC activity. There were no significant differences in the levels of FcgammaRI expression or ADCC activity between the 2 microg/kg G-CSF and 5 microg/kg G-CSF groups, indicating that the optimal dose of G-CSF was 2 microg/kg.
  
  
  CONCLUSIONS
  We conclude that the combination of rituximab-CHOP and G-CSF is well tolerated. We plan to carry out a randomized trial to compare efficacy between rituximab-CHOP treatment and treatment with a combination of rituximab-CHOP and G-CSF.
authors.affiliation: Department of Hematology and Internal Medicine IV, Kitasato University School of Medicine, Kanagawa, Japan. nniitsu@med.kitasato-u.ac.jp
authors.forename: Nozomi
authors.initials: N
authors.lastname: Niitsu
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hayama
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.forename: Mika
authors.initials: M
authors.lastname: Khori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tamaru
authors.forename: Masami
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D000941:Antigens / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002462:Cell Membrane / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use*; D017452:Receptors, IgG / Q000096:biosynthesis; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000941:Antigens; D017452:Receptors, IgG; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D011239:Prednisolone