Background: Achievement of a complete (CR) or partial (PR) response at the PTS to IC with cisplatin and 5-FU correlates with disease control after subsequent definitive radiation-based therapy (RT) in patients with HNSCC. The likelihood of CR/PR after IC is high in T_1/2 and low in T_3/4 tumors. SPARC, an albumin binding protein that is commonly overexpressed in HNSCC, may facilitate preferential accumulation of nab-paclitaxel at PTS compared to other formulations of taxanes. Methods: The primary objective of the prospective phase II trial was to determine the clinical CR and PR rate at the PTS to an IC regimen of weekly nab-paclitaxel (100 mg/m²) and cetuximab (250 mg/m²) with every 3 week cisplatin (75 mg/m²) and 5-FU (750 mg/m² per day x3 CIVI) (ACCF) given for two cycles in patients with HNSCC. PTS response assessment was performed by clinical exam using categorical outcomes [CR: 100%↓, near CR: 95%↓, PR: 50-94%↓, or progression]. All patients were treated with a third cycle of ACCF, then definitive chemo-RT. These outcomes were compared to retrospective data from a cohort of 58 patients treated with TPF+C. Results: Thirty patients were enrolled on the prospective trial and all were evaluable for the primary objective. Most (73%) had bulky T_3/4 primary tumors. PTS response to ACCF is shown in the table: CR/near CR: 16 patients (53%) and PR: 14 patients (47%). In the retrospective analysis, most (83%) had bulky primary tumors. The PTS response to TPF+C was CR: 15 patients (27%), PR: 31 patients (56%), and progression: 9 patients (16%). Conclusions: ACCF is a novel IC regimen that resulted in a high likelihood of a favorable (CR/PR) PTS response in patients with high T stage HNSCC. These outcomes compare favorably to our historical experience with TPF+C.

* PTS assessment by exam and/or imaging.