Designation Products: Boron Neutron Capture Therapy for Head and Neck Carcinoma

Abstract

The Ministry of Health, Labour and Welfare approved a drug called Borofalan (¹⁰B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) in March 2020. The application pertaining to the products submitted to the Pharmaceuticals and Medical Devices Agency was supported by a Japanese open‐label uncontrolled trial (Study 002) in patients with unresectable locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiotherapy, or in those with unresectable locally advanced or locally recurrent (LA/LR) head and neck non‐squamous cell carcinoma. The drug was administered as a single intravenous dose using infusion rates of 200 mg/kg/h for the first two hours after the start of administration and 100 mg/kg/h during irradiation. Neutrons irradiation was performed using the devices at a single dose of 12 Gy‐Eq. for oral, pharyngeal, or laryngeal mucosa for up to 60 minutes from two hours after the start of drug administration. The primary endpoint was the overall response rate (ORR). The results of Study 002 showed that the ORR [90% confidence interval (CI)] (%) based on an assessment of the Independent Central Review Committee per Response Evaluation Criteria in Solid Tumors (RECIST) ver.1.1 was 71.4 [51.3, 86.8]. The lower limit of the 90% CI exceeded the pre‐specified threshold for ORR. When BNCT is applied to patients with unresectable LA/LR head and neck cancer, precautions should be taken, and patients should be monitored for possible onset of dysphagia, brain abscess, skin disorder, crystal urine, cataract, and/or carotid hemorrhage. Implications for Practice Borofalan (¹⁰B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) have demonstrated significant efficacy based on the result of an open‐label uncontrolled trial (Study 002) in which the overall response rate was determined as the primary endpoint for patients with unresectable locally advanced or locally recurrent head and neck cancer. Although no information about survival benefits has been obtained, the BNCT will become an effective treatment option that is expected to manage local lesions that are intractable with any standard therapy. In addition, the BNCT is expected to maintain the quality of life of the intended patient population, on account of its high tumor selectivity and low invasiveness.