Background: Standard of care treatments for locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) are not well tolerated, particularly in elderly or frail patients. One combination that has been studied in recent years is paclitaxel, carboplatin and cetuximab (PCC). Studies have shown this regimen yields promising results when used as an induction chemotherapy for locally advanced disease. PCC has also been studied in patients with metastatic or recurrent incurable disease, and has shown good response with tolerable toxicity rates, but there is a relative dearth of evidence surrounding its use. Methods: This retrospective observational study utilized EMR data analysis software to generate the cohort of adult patients that received PCC for HNSCC in 2014-2019 as well as demographic data. Chart review was used to gather details about the patients’ tumors and clinical course. Modified RECIST response rates (MRRR), progression free survival (PFS) and overall survival (OS) were the primary end points calculated for the metastatic/recurrent group, and percentage of successful inductions (e.g., patients went on to definitive treatment, avoided surgery) and MRRR were used for the induction group. Results: There were 80 patients in the cohort. The average age was 65 (range 33-84) and the patients were 81% male. The most common tumor site was the tongue (25 patients), followed by tonsil (15), oropharynx (9), and larynx (7). 13 patients had p16 positive disease. Most patients had Stage IVA (36 patients), followed by IVB (20), and IVC (15); the remainder had stage III or below or unknown stage. The most common reasons patients did not receive cisplatin were performance status (13 patients), hearing loss (11), concern for nephrotoxicity (6) and age (5). 97.5% of patients experienced at least one adverse effect. The most common adverse effect was dermatologic (69%), followed by hematologic (51%), fatigue (41%) and gastrointestinal symptoms (41%). 53 patients (66%) experienced at least one dose interruption due to adverse effects. 11 patients (14%) stopped treatment due to toxicities. 58 patients received PCC for metastatic or recurrent disease. They had received a median of 1 line of systemic treatment prior; 72% had prior radiation, and 26% had prior salvage surgery. The MRRR was 22% (5 patients with complete response, 8 partial response, 15 stable, 27 progression). There was a 7.0 month mean PFS, and 17.3 month mean OS. Of the 22 patients who received PCC as induction, 86% (19) successfully reached their induction endpoint. The MRRR was 64% (8 patients with complete response, 6 partial response). Conclusions: PCC is a relatively well-tolerated combination with a very good induction success rate. More research is needed around alternate options for frail and elderly patients with HNSCC.