Nine patients showed clinical PR, 10 showed Pevonedistat in vivo SD, and 2 showed PD. The clinical response rate (CR or PR) of the neck disease was 42.9%. Table 4 Clinical response of the neck disease CR PR SD PD Response rate Level 1 1 1 50% Level 2 1 1 0% Level 3 1 2 33.3% Level 4 2 1 66.7% Level 5 3 0% Level 6 1 1 1 33.3% Level 7
3 100% Level 8 1 1 50% Total 9 10 2 42.9% Abbreviations: CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease After surgery, local failure developed in one patient (level 6), and neck failure and distant metastasis occurred in another (level 7). With a median follow-up of 67 months, the 5-year overall survival rate was 90.0%, and the 5-year cumulative survival was 93.1%. Discussion We set out to determine the safety and
reliability of concurrent S-1 and radiotherapy in advanced cancer of the oral cavity, in a phase I study. Many studies have demonstrated that combined chemotherapy selleck kinase inhibitor and radiation is a highly effective treatment modality for increasing the survival of patients with advanced disease [2, 3, 9–11]. Concurrent chemoradiotherapy has been established as an appropriate selleck chemicals standard for many patients with locally advanced head and neck cancer. To the best of our knowledge, this study is the first trial of S-1 and radiotherapy in oral cancer. Tsukuda et al. reported that most adverse events of S-1 administration alone were hematological, RVX-208 gastrointestinal, and skin toxicities, although most of these were grade 1 or 2 and controllable [12]. In the present study, there was no severe hematological, gastrointestinal, or skin toxicity. Mucositis was the most common adverse event, with grade 3 mucositis observed in 66.7% of patients at levels 5, 6, and 7 (Additional file 1). Grade 4 mucositis, constituting DLT, was observed in 2 of 6 patients at level 8. The doses used level 8 was deemed the MTD. Therefore, the determined recommended dose of S-1 was the reduced dose for 5 days
per week for 4 weeks (level 7). In a multi-institutional cooperative late phase II clinical study of S-1 alone in patients with advanced/recurrent head and neck cancer in Japan, the clinical response rate of the primary tumor was 36.4% in oral cancer patients [13]. In the present study, the overall clinical response rate was 93.3%, and the histological response rate was 90.0%, appearing to be remarkably good. Many studies have demonstrated concurrent chemoradiotherapy to be effective in patients with advanced head and neck cancer. However, the majority of studies have reported total radiation doses of more than 60-Gy. Tsukuda et al. reported that the complete response rate were 93% in stage III and 54% in stage IV, by treating head and neck cancer with S-1 and radiotherapy at a total dose of 66-70.2 Gy [14]. There have been few reports on the effect of preoperative chemoradiotherapy with a total radiation dose of 40-Gy [2, 3].