Eiji Oki1, Takeshi Kato2, Hideaki Bando3, Takayuki Yoshino3, Kei Muro4, Hiroya Taniguchi4, Yoshinori Kagawa5, Kentaro Yamazaki6, Tatsuro Yamaguchi7, Akihito Tsuji8, Shigeyoshi Iwamoto9, Goro Nakayama10, Yasunori Emi11, Tetsuo Touyama12, Masato Nakamura13, Masahito Kotaka14, Hideki Sakisaka15, Takeharu Yamanaka16, Akiyoshi Kanazawa17. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. Electronic address: ken-kato@momo.so-net.ne.jp. 3. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan. 4. Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan. 5. Department of Colorectal Surgery, Kansai Rosai Hospital, Hyogo, Japan. 6. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 8. Department of Medical Oncology, Kagawa University Hospital, Kagawa, Japan. 9. Cancer Center, Aichi Medical University, Aichi, Japan. 10. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Aichi, Japan. 11. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan. 12. Department of Surgery, Nakagami Hospital, Okinawa, Japan. 13. Aizawa Comprehensive Cancer Center, Aizawa Hospital, Nagano, Japan. 14. Gastrointestinal Cancer Center, Sano Hospital, Hyogo, Japan. 15. Department of Surgery, Kawanishi City Hospital, Hyogo, Japan. 16. Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan. 17. Department of Surgery, Shimane Prefectural Central Hospital, Shimane, Japan.
Abstract
BACKGROUND: FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. PATIENTS AND METHODS: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. RESULTS: A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P = .004). CONCLUSIONS: FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.
BACKGROUND:FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. PATIENTS AND METHODS: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. RESULTS: A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P = .004). CONCLUSIONS:FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.
Authors: Haeseong Park; Ramon U Jin; Andrea Wang-Gillam; Rama Suresh; Caron Rigden; Manik Amin; Benjamin R Tan; Katrina S Pedersen; Kian-Huat Lim; Nikolaos A Trikalinos; Abhilasha Acharya; Megan L Copsey; Katherine A Navo; Ashley E Morton; Feng Gao; A Craig Lockhart Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777