Phase I study of Rituximab-CHOP regimen in combination with granulocyte colony-stimulating factor in patients with follicular lymphoma.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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: Nozomi Niitsu, Miyuki Hayama, Masataka Okamoto, Mika Khori, Masaaki Higashihara, Jun-Ichi Tamaru, Masami Hirano
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 12 Pt 1 Pg. 4077-82 (Jun 15 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15217942 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antigens
• Receptors, IgG
• Interleukin-10
• Granulocyte Colony-Stimulating Factor
• Interleukin-4
• Rituximab
• Vincristine
• Doxorubicin
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cyclophosphamide
• Prednisolone

Topics

• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antibody-Dependent Cell Cytotoxicity
• Antigens (chemistry)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Membrane (metabolism)
• Cyclophosphamide (therapeutic use)
• Doxorubicin (therapeutic use)
• Female
• Granulocyte Colony-Stimulating Factor (metabolism, therapeutic use)
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• Humans
• Immunophenotyping
• Interleukin-10 (blood)
• Interleukin-4 (blood)
• Lymphoma, Follicular (drug therapy)
• Male
• Middle Aged
• Neutrophils (metabolism)
• Prednisolone (therapeutic use)
• Receptors, IgG (biosynthesis)
• Rituximab
• Time Factors
• Treatment Outcome
• Vincristine (therapeutic use)