Background: Neoadjuvant chemotherapy (NACT) in head and neck cancers (HNC) with taxane, platinum, 5-FU (TPF) regimen is both toxic as well as difficult to use in resource-constrained settings. We used a novel combination of weekly chemotherapy and oral metronomic chemotherapy (OMCT) and assessed the efficacy and safety of this combination as NACT in locally advanced HNC patients. Methods: This is a retrospective analysis of prospectively maintained data. 56 patients with technically unresectable HNC received NACT with paclitaxel (80mg/m2) plus carboplatin (AUC2) - weekly schedule and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily, and erlotinib 150mg once daily) - PCm regimen. Patients were assessed clinically and radiologically after a minimum of six cycles for resectability. The radiological response was evaluated as per RECIST 1.1. We report the response rate, resectability, survival, and tolerance of this NACT regimen. Results: The median age of the patients was 41 years. Fifty-two patients (92.9%) were male. Buccal mucosa (60.7%) and oral tongue (17.9%) were the commonest sites of primary seen followed by alveolus (10.7%), the floor of mouth (5.4%), and larynx (5.4%). AJCC 2017 stage IVA and IVB disease were present in 64.3% and 35.7% of patients respectively. Edema up to zygoma (44.6%), high ITF involvement (19.7%), technically unresectable nodal disease (16.1%) and disease reaching up to vallecula (12.5%), or hyoid bone (5.4%), and nodal encasement (180-270 degree) of the internal carotid artery (1.8%) were the reasons for technical unresectability. The median number of NACT administered was six. The tumor showed partial response in 54 (96.4%) patients, 2 (3.6%) patients had stable disease and none of the patients had tumor progression. Surgery was planned in 47 (83.9%) patients after NACT, however due to logistic issues only 35 (62.5%) patients could undergo surgery. Pathological complete response was seen in 27 (48.21%) patients. After a median follow-up of 7.36 months, median PFS was not reached in the whole cohort and surgery group of patients, whereas it was 5.23 (95% CI, 4.08 -6.38) months in the non-surgery group. Median OS was not reached in our cohort. Common grade 3/4 toxicities (CTCAE 5.0) observed were oral mucositis in 6 (10.7%) patients, diarrhea in 4 (7.1%), and febrile neutropenia in 1 (1.7%) patients. Conclusions: Weekly scheduled PCm is an efficacious and well-tolerated regimen and can easily be administered in resource-constrained settings.