Kanemitsu Yukihide, Shimizu Yasuhiro, Mizusawa Junki, Inaba Yoshitaka, Hamaguchi Tetsuya, Shida Dai, Ohue Masayuki, Komori Koji, Shiomi Akio, Shiozawa Manabu, Watanabe Jun, Suto Takeshi, Kinugasa Yusuke, Takii Yasumasa, Bando Hiroyuki, Kobatake Takaya, Inomata Masafumi, Shimada Yasuhiro, Katayama Hiroshi, Fukuda Haruhiko
National Cancer Center Hospital, Tokyo, Japan.
Aichi Cancer Center Hospital, Nagoya, Japan.
J Clin Oncol. 2021 Dec 1;39(34):3789-3799. doi: 10.1200/JCO.21.01032. Epub 2021 Sep 14.
Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.
Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.
DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
肝切除术后辅助化疗在单纯肝转移结直肠癌（CRC）中存在争议。我们进行了一项随机对照试验，以检验辅助性改良氟尿嘧啶持续静脉滴注、亚叶酸钙和奥沙利铂（mFOLFOX6）对于CRC单纯肝转移是否优于单纯肝切除术。
在这项II期或III期试验（JCOG0603）中，年龄20 - 75岁、确诊为CRC且肝转移灶数量不限的患者被随机分配至单纯肝切除术组或肝切除术后接受12个疗程辅助性mFOLFOX6治疗组。III期的主要终点是意向性分析中的无病生存期（DFS）。
2007年3月至2019年1月期间，300例患者被随机分配至单纯肝切除术组（149例患者）或肝切除术后化疗组（151例患者）。在III期的第三次中期分析中，中位随访时间为53.6个月，由于肝切除术后化疗患者的DFS显著更长，该试验按照方案提前终止。中位随访59.2个月时，单纯肝切除术组更新后的5年DFS为38.7%（95%CI，30.4至46.8），而化疗组为49.8%（95%CI，41.0至58.0）（风险比，0.67；95%CI，0.50至0.92；单侧P = 0.006）。然而，单纯肝切除术组更新后的5年总生存期（OS）为83.1%（95%CI，74.9至88.9），肝切除术后化疗组为71.2%（95%CI，61.7至78.8）。在化疗组中，最常见的3级或更高严重不良事件是中性粒细胞减少（50%的患者），其次是感觉神经病变（10%）和过敏反应（4%）。1例患者在接受三个疗程的mFOLFOX6治疗后死于不明原因。
对于单纯肝转移的CRC，DFS与OS不相关。mFOLFOX6辅助化疗可改善CRC肝转移患者肝切除术后的DFS。化疗是否能改善OS仍不清楚。
