Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0

Abstract

Background: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment. But this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). We herein report the results of the efficacy confirmation phase in the T4a cohort.Patients and methods: Patients received cisplatin 100 mg/m2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (3yr OS), comparing RADPLAT with the historical control for 3yr OS in surgery (80%).Results: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After excluding one ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (≥ grade 3), neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), and stroke (≥ grade 2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported.Conclusion: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 MS-SCCs compared with the historical control for 3yr OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.