Safety and antitumor activity of accelerator-based boron neutron capture therapy in patients with inoperable recurrent and locally advanced head and neck cancer: A phase II study.

Abstract

6028 Background: To assess safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent squamous cell carcinoma (R-HNSCC) or recurrent/locally advanced non-squamous cell carcinoma (R/LA-HNNSCC) of the head and neck. Methods: The multi-institutional open-label, a world-first phase II trial of AB-BNCT in patients with inoperable R-HNSCC which present resistance to platinum-based chemotherapy, or with inoperable R/LA-HNNSCC, was conducted to assess safety and antitumor activity of AB-BNCT with BNCT30 and SPM-011. SPM-011 was administered at 200 mg/kg/h intravenously for 2 hours, followed by neutron irradiation with continuous infusion of SPM-011 at 100 mg/kg/h. The irradiated dose for tumor was determined passively as a mucosal maximum dose was given 12 Gy-Eq in calculation with a blood boron concentration measured just before the start of neutron irradiation. Primary endpoint was objective response rate (ORR) by central review. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 every 4 weeks for the first 3 months and every 12 weeks thereafter. Results: Eight R-HNSCC and thirteen R/LA-HNNSCC patients were enrolled and received AB-BNCT. All R-HNSCC patients had prior radiotherapy with a median dose of 65.5 Gy (range 59.4–76.0). The median irradiation time was 43 min (range 26–65). The median tumor minimum dose was 31.0 Gy-Eq (range 16.1–42.6). For adverse event, nausea (81%), dysgeusia (71%), parotitis (67%) were observed more frequently. The ORR for all patients were 71.4%, and CR/PR were 50.0%/25.0% in R-HNSCC and 7.7%/61.5% in R/LA-HNNSCC. At a median follow up of 18.8 months (range 9.2–29.0), 1-year PFS and OS by investigator assessment were 70.6% and 100%, respectively. The data for antitumor activity is still immature and will be further updated. Conclusions: AB-BNCT for R-HNSCC and R/LA-HNNSCC demonstrated an acceptable safety profile and a promising antitumor activity.