Combined Nimotuzumab with Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Abstract

Background Most head and neck cancers (HNCs), specifically squamous cell carcinoma, express epidermal growth factor and are associated with an inadequate response to radiotherapy and chemotherapy. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) increase response rates and survival when combined with radiotherapy or chemoradiotherapy (CRT). This study evaluates the outcome and toxicity of the nimotuzumab-CRT combination for stage III, IVa, and IVb squamous cell carcinoma of the head and neck. Methods Eighty-seven patients with squamous cell carcinoma of the head and neck, stage III, IVa, or IVb were enrolled in a prospective comparative study. The nimotuzumab plus CRT group consisted of patients who received nimotuzumab 200 mg every week for six consecutive weeks chemoradiation therapy; cisplatin 30 mg/m 2 every week for six weeks; radiotherapy of 2-Gy/fraction, five fractions/week for a total dose of 70 Gy; and neck lymph node invasion prophylaxis at 50 Gy. The CRT alone arm was treated with CRT (without nimotuzumab). Results Tumor response rate of 90.6% was achieved in nimotuzumab plus CRT group (complete response: 58.1%), and 70.4% in CRT alone arm (complete response: 38.6%; p=0.029). The lymph node response rate was 83.4% in nimotuzumab plus CRT group (complete response: 46.7%), and 73.0% in CRT group (complete response: 23.0%). The general response rate in nimotuzumab plus CRT group was 86.0% (complete response: 48.8%), and 68.0% in CRT alone arm (complete response: 36.0%). Twelve-month overall survival (OS) was 75.1% for the nimotuzumab plus CRT group and 54.4% for the CRT group. The 24-month survival was 48.0% (nimotuzumab plus CRT group) and 29.0% (CRT alone arm). The median OS was 20 months and 13 months for nimotuzumab plus CRT group and CRT alone arm, respectively. Progression-free survival (PFS) in the nimotuzumab plus CRT group at 12 months and 24 months was 64.2% and 37.4%, respectively. PFS in the CRT group at 12 months and 24 months was 39.5% and 21.3%, respectively. Infusion reaction presented mildly in two of 43 patients in the nimotuzumab plus CRT group, and no shock occurred. Other toxicity occurrences were similar between the two groups, mainly in grade I, II. Skin rash (grade I only) occurred at a rate of 4.7% in the nimotuzumab plus CRT group. Conclusion 1 2

Combined Efficacy of Nimotuzumab and Gemcitabine on the Treatment of Advanced Pancreatic cancer

“…14 A foreign study pointed out that nituzumab can reduce the nutrient supply of tumor cells and promote apoptosis by downregulating the expression of vascular endothelial growth factor in tumor in situ mouse models. 15 Based on a recent study, nimotuzumab can also promote apoptosis by downregulating the expression of vascular endothelial growth factor in tumor in situ mouse models, reducing the nutritional supply of tumor cells. 16 In addition, it can activate antibody-dependent cell-mediated cytotoxic effects and complement-dependent cytotoxic effects, effectively killing tumor cells.…”

“…Based on good foreign data, the 2020 edition of CSCO Pancreatic Cancer Diagnosis and Treatment Guidelines recommends nituzumab to fit GEM as a first-line chemotherapy regimen for advanced pancreatic cancer 14 . A foreign study pointed out that nituzumab can reduce the nutrient supply of tumor cells and promote apoptosis by downregulating the expression of vascular endothelial growth factor in tumor in situ mouse models 15 . Based on a recent study, nimotuzumab can also promote apoptosis by downregulating the expression of vascular endothelial growth factor in tumor in situ mouse models, reducing the nutritional supply of tumor cells 16 .…”

“…Fully humanized IgG monoclonal antibody, nituzumab, is a widely used molecular targeted drug, which can competitively bind EGFR and inhibit its downstream signaling pathway activity. 7 In vivo, nituzumab can also induce antibody-dependent cell-mediated cytotoxic effects and complement-mediated cytotoxic effects to kill tumor cells. Compared with other EGFR antibodies, nituzumab has a moderate affinity with EGFR, with a dissociation constant of 4.53 Â 10-8 M, which is conducive to binding of the antibody to tumor cell surface receptors.…”

“…Her/erbB receptor family is the main target of molecular targeted therapy in pancreas and has shown certain efficacy in phase II and III clinical trials. Fully humanized IgG monoclonal antibody, nituzumab, is a widely used molecular targeted drug, which can competitively bind EGFR and inhibit its downstream signaling pathway activity 7 . In vivo, nituzumab can also induce antibody-dependent cell-mediated cytotoxic effects and complement-mediated cytotoxic effects to kill tumor cells.…”

Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials

“…We preliminarily identified 1146 relevant articles from the database. After removing 352 duplicate literatures, we evaluated and screened the title, abstract or full text according to strict inclusion and exclusion criteria, and finally included 7 eligible RCT for meta-analysis (16)(17)(18)(19)(20)(21)(22). The detailed screening procedure is shown in Figure 1.…”