caa a22 4500 605491194 CHVBK 20210128100508.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s10147-015-0784-9 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0784-9 Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study [Elektronische Daten] [Eiji Oki, Yasunori Emi, Hiroshi Kojima, Jun Higashijima, Takeshi Kato, Yasuhiro Miyake, Masanori Kon, Yutaka Ogata, Kenichi Takahashi, Hideyuki Ishida, Hiroshi Saeki, Yoshihisa Sakaguchi, Takeharu Yamanaka, Toru Kono, Naohiro Tomita, Hideo Baba, Ken Shirabe, Yoshihiro Kakeji, Yoshihiko Maehara] Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG's potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6% in the GJG group and 31.2% in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p=0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated. Japan Society of Clinical Oncology, 2015 Adjuvant chemotherapy nationallicence Colon cancer nationallicence Colorectal cancer nationallicence Goshajinkigan nationallicence Herbal medicine, Kampo nationallicence Peripheral neuropathy nationallicence Oki Eiji Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut Emi Yasunori Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan aut Kojima Hiroshi Department of Gastroenterological Surgery, Aichi Cancer Center Aichi Hospital, Nagoya, Japan aut Higashijima Jun Department of Digestive and Pediatric Surgery, Faculty of Medicine, University of Tokushima, Tokushima, Japan aut Kato Takeshi Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan aut Miyake Yasuhiro Department of Surgery, Minoh City Hospital, Minoh, Japan aut Kon Masanori Department of Surgery, Kansai Medical University, Osaka, Japan aut Ogata Yutaka Department of Surgery, Kurume University Medical Center, Kurume, Japan aut Takahashi Kenichi Department of Surgery, Aomori Prefectural Central Hospital, Aomori, Japan aut Ishida Hideyuki Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical School, Saitama, Japan aut Saeki Hiroshi Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut Sakaguchi Yoshihisa Department of Gastroenterological Surgery, Kyushu National Medical Center, Fukuoka, Japan aut Yamanaka Takeharu Department of Biostatistics, Yokohama City University, Yokohama, Japan aut Kono Toru Sapporo Higashi Tokushukai Hospital, Sapporo, Japan aut Tomita Naohiro Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan aut Baba Hideo Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan aut Shirabe Ken Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut Kakeji Yoshihiro Department of Gastrointestinal Surgery, Kobe University, Kobe, Japan aut Maehara Yoshihiko Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut International Journal of Clinical Oncology Springer Japan 20/4(2015-08-01), 767-775 1341-9625 20:4<767 2015 20 10147 https://doi.org/10.1007/s10147-015-0784-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0784-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Oki Eiji Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Emi Yasunori Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kojima Hiroshi Department of Gastroenterological Surgery, Aichi Cancer Center Aichi Hospital, Nagoya, Japan aut NATIONALLICENCE 700 1- Higashijima Jun Department of Digestive and Pediatric Surgery, Faculty of Medicine, University of Tokushima, Tokushima, Japan aut NATIONALLICENCE 700 1- Kato Takeshi Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan aut NATIONALLICENCE 700 1- Miyake Yasuhiro Department of Surgery, Minoh City Hospital, Minoh, Japan aut NATIONALLICENCE 700 1- Kon Masanori Department of Surgery, Kansai Medical University, Osaka, Japan aut NATIONALLICENCE 700 1- Ogata Yutaka Department of Surgery, Kurume University Medical Center, Kurume, Japan aut NATIONALLICENCE 700 1- Takahashi Kenichi Department of Surgery, Aomori Prefectural Central Hospital, Aomori, Japan aut NATIONALLICENCE 700 1- Ishida Hideyuki Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical School, Saitama, Japan aut NATIONALLICENCE 700 1- Saeki Hiroshi Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Sakaguchi Yoshihisa Department of Gastroenterological Surgery, Kyushu National Medical Center, Fukuoka, Japan aut NATIONALLICENCE 700 1- Yamanaka Takeharu Department of Biostatistics, Yokohama City University, Yokohama, Japan aut NATIONALLICENCE 700 1- Kono Toru Sapporo Higashi Tokushukai Hospital, Sapporo, Japan aut NATIONALLICENCE 700 1- Tomita Naohiro Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan aut NATIONALLICENCE 700 1- Baba Hideo Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan aut NATIONALLICENCE 700 1- Shirabe Ken Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kakeji Yoshihiro Department of Gastrointestinal Surgery, Kobe University, Kobe, Japan aut NATIONALLICENCE 700 1- Maehara Yoshihiko Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/4(2015-08-01), 767-775 1341-9625 20:4<767 2015 20 10147