Background: Neoadjuvant chemotherapy with TPF though the standard is seldom used in India due to its adverse events rate. Two drug regimen of Paclitaxel and Carboplatin (PC) though favoured has inferior outcomes. Hence, we did an analysis to estimate the efficacy and adverse event rate of addition of 3 drug metronomic schedule to PC. Methods: Patients of locally advanced head and neck cancer referred from multidisciplinary board for neoadjuvant chemotherapy and unsuitable for TPF were selected for this analysis. These patients had received 2 drug regimen of intravenous PC with 3 drug regimen of weekly methotrexate 9 mg per m2, Celecoxib 200 mg twice daily, erlotinib 150 mg once daily all administered orally. All patients underwent a response assessment at 5-7 weeks post start of therapy and we're discussed in MDT for further treatment. Adverse events were recorded in accordance with CTCAE version 4.03 and response in accordance with RECIST version 1.1. PFS and OS were estimated with Kaplan Meier method. Results: 72 patients were identified with the median age being 45 (27-80) and M:F ratio (67:5). The indication for NACT were borderline resectability in all patients.. The response rate was 61.1% and grade 3 and above adverse event rate was 33.5%. A total number of 34 among 40 borderline resectable patients underwent surgery. The overall estimated PFS and OS were 18.5 (95%CI = 14.4-22.7) months and 18.05 (95%CI = 14.2-21.8) months respectively. The three most adverse events observed were grade 3 thrombocytopenia in 2 patients (2.8%), grade 3 aspartate aminotransferase (AST) derangement in 4 patients (5.6%) and grade 3 alanine aminotransferase (ALT) in 4 patients (5.6%). Conclusions: The 5 drug combination regimen is safe, tolerable and seems to have similar efficacy as a three drug TPF regimen.