Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck

Background The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. Methods Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m 2 /day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m 2 , followed by 250 mg/m 2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49–82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22–66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0–18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1–8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). Conclusions Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number : UMIN000015123