A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN

Abstract

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2 days 1–5, and cetuximab 250mg/m2 days 1, 8, and 15 (initial dose 400mg/m2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received <2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]