Masuishi Toshiki, Taniguchi Hiroya, Hamauchi Satoshi, Komori Azusa, Kito Yosuke, Narita Yukiya, Tsushima Takahiro, Ishihara Makoto, Todaka Akiko, Tanaka Tsutomu, Yokota Tomoya, Kadowaki Shigenori, Machida Nozomu, Ura Takashi, Fukutomi Akira, Ando Masashi, Onozawa Yusuke, Tajika Masahiro, Yasui Hirofumi, Muro Kei, Mori Keita, Yamazaki Kentaro
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Clin Colorectal Cancer. 2017 Jun;16(2):e15-e22. doi: 10.1016/j.clcc.2016.07.019. Epub 2016 Aug 31.
Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first.
We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti-epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102.
A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa.
Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice.
瑞戈非尼和曲氟尿苷/替匹嘧啶（TAS-102）均可延长难治性转移性结直肠癌患者的生存期。然而，尚不清楚应首先使用哪种药物。
我们回顾性评估了2013年5月至2015年3月在2家机构接受瑞戈非尼或TAS-102治疗的患者的数据。纳入标准为对氟嘧啶、奥沙利铂、伊立替康、抗血管内皮生长因子抗体及抗表皮生长因子受体（EGFR）抗体（若KRAS第2外显子为野生型）难治或不耐受的疾病，且既往未接受过瑞戈非尼或TAS-102治疗。
分别有146例和54例患者接受了瑞戈非尼和TAS-102治疗。两组的基线特征相似，但伊立替康和抗EGFR治疗史以及碱性磷酸酶水平较高的情况除外。瑞戈非尼组的中位无进展生存期和总生存期分别为2.1个月和6.7个月，TAS-102组分别为2.1个月和6.5个月（无进展生存期风险比1.20，P = 0.27；总生存期风险比1.01，P = 0.97）。在日本批准TAS-102后对患者总生存期的分析与对整个人群的总生存期分析相似。瑞戈非尼组手足综合征、天冬氨酸转氨酶、丙氨酸转氨酶和胆红素水平升高的发生率高于TAS-102组，而中性粒细胞减少、白细胞减少、贫血、恶心和发热性中性粒细胞减少的发生率低于TAS-102组。在既往接受过或未接受过瑞戈非尼治疗的患者中，TAS-102的疗效和安全性未发现显著差异，反之亦然。
瑞戈非尼和TAS-102疗效相似，但毒性不同，这可为药物选择提供指导。
