Phase I study of Rituximab-CHOP regimen in combination with granulocyte colony-stimulating factor in patients with follicular lymphoma.
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.
Niitsu
Nozomi
N
Department of Hematology and Internal Medicine IV, Kitasato University School of Medicine, Kanagawa, Japan. nniitsu@med.kitasato-u.ac.jp
Hayama
Miyuki
M
Okamoto
Masataka
M
Khori
Mika
M
Higashihara
Masaaki
M
Tamaru
Jun-Ichi
J
Hirano
Masami
M
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*
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