Role of Humanized EGFR Monoclonal Antibody as Induction Chemotherapy in Advanced Head and Neck Cancer along with Chemo-Radiation

Abstract

Background: World-wide Head and neck cancer (HNC) forms the sixth most common cancer. It is the most common cancer of males and fifth most common in females in India. It's mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). Chemoradiation is the standard of care in locally advanced disease. A few randomized trials have demonstrated improved response rate, disease free survival, and overall survival with induction chemotherapy. Epidermal Growth Factor Receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation, and resistance to apoptosis. Nimotuzumab is a humanized monoclonal antibody targeting EGFR. This study is to evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in HNSCC patients. Method(s): We retrospectively analyzed the results of this open-label, single arm study. 52 patients were enrolled for the study after the approval of ethical committee of our hospital. Patients above 18 years old with histologically confirmed advanced HNSCC were included. Patients were treated with 3 cycles of induction chemotherapy consisting of modified TPF regimen (reduced doses of Docetaxel, Cisplatin, & 5-FU) along with nimotuzumab (200 mg IV) on day 1, followed by radiotherapy for a dose of 66 Gy along with concurrent weekly cisplatin (30 mg/m2) and nimotuzumab (200 mg) throughout the course of radiation. Patients were evaluated using RECIST criteria, 6 weeks after the last cycle of chemotherapy. Result(s): 52 patients were included in this study with mean age of 47616 years. Most common sub-site of cancer was oral cavity in 84.6% (n=44), followed by pharynx in 15.4% (n=8). 18 patients (34.6%) had metastasis at the time of presentation. 27 patients (51.9%) had progressive disease and 7 patients (13.46%) were lost to followup. All patients completed 3 cycles of induction chemotherapy with TPF regimen and nimotuzumab. 40 (76.9%) patients completed 6 cycles of concurrent chemoradiotherapy with cisplatin. 21 patients (40.3%) achieved complete response and are disease free. The median duration of response was 37 months (18- 61 months). The combination chemotherapy with nimotuzumab was well tolerated. Addition of nimotuzumab to TPF regimen was not associated with added toxicity. Conclusion(s): The frequent somatic alteration and/or overexpression of EGFR in malignant cells compared to normal cells provides a therapeutic window for targeting the receptor. Addition of anti-EGFR monocloncal antibody (nimotuzumab) to induction chemotherapy and chemo-radiation may be a promising alternative to concurrent chemo-radiotherapy in HNSCC due to known over expression of EGFR receptors. The results of this study need further evaluation in a larger study setting. It's essential to understand tumor biology to improve molecular diagnostics and therapeutics and development of novel therapies in future.