Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial
Kiyota, Naomi, 清田, 尚臣, キヨタ, ナオミ, Tahara, Makoto, Mizusawa, Junki, Kodaira, Takeshi, Fujii, Hirofumi, Yamazaki, Tomoko, Mitani, Hiroki, Iwae, Shigemichi, Fujimoto, Yasushi, Onozawa, Yusuke, Hanai, Nobuhiro, Ogawa, Takenori, Hara, Hiroki, Monden, Nobuya, Shimura, Eiji, Minami, Shujiro, Fujii, Takashi, Tanaka, Kaoru, Homma, Akihiro, Yoshimoto, Seiichi, Oridate, Nobuhiko, Omori, Koichi, Ueda, Tsutomu, Okami, Kenji, Ota, Ichiro, Shiga, Kiyoto, Sugasawa, Masashi, Asakage, Takahiro, Saito, Yuki, Murono, Shigeyuki, Nishimura, Yasumasa, Nakamura, Kenichi, Hayashi, Ryuichi, the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group (JCOG-HNCSG)
Abstract
PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.