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背景和目的肝脏是结直肠癌最常见的远处转移部位。大约半数结肠癌患者病程中会发生肝转移。以往多数围绕靶向药物西妥昔单抗的临床研究通常仅关注KRAS突变状态对治疗的影响以及与多种化疗方案联合的治疗效果,几乎未有研究探讨其是否有利于提高肝转移二期切除的转化率。因此,该研究针对无法切除的KRAS野生型结肠癌同时性单纯肝转移(CLM)患者,评价西妥昔单抗联合化疗方案用于一线治疗对根治性肝切除的效果,同时了解肿瘤缓解情况和患者总生存情况。对象和方法同时存在结肠癌并无法切除、有限的肝转移情况的KRAS野生型患者,在接受原发肿瘤切除治疗后,随机分配接受化疗FOLFIRI(氟尿嘧啶、亚叶酸及伊立替康)或mFOLFOX6(改良的氟尿嘧啶、亚叶酸及奥沙利铂方案)联合西妥昔单抗方案(A组)或单纯化疗方案(B组)治疗。该研究主要终点为治疗后肝转移可进行手术切除的转化率。次要终点为客观缓解率及生存率。结果意向治疗人群共有138例患者;其中70例患者被随机分配至A组,68例患者被分配至B组。随访中位时间25.0个月,全部患者的3年总生存(OS)率及中位生存时间(MST)为30%及24.4个月。A组肝转移患者R0切除率为25.7%(18/70),B组则为7.4%(5/68),组间差异有统计学意义(P<0.01)。18例接受肝切除的患者中,术前中位化疗6周期(4~12周期);其中11例行多个肝楔形切除,4例右半肝切除,3例左半肝切除。术后无严重并发症。A组患者与B组相比,其客观缓解率和3年OS率更高(分别为57.1%和29.4%,P<0.01;及41%和18%,P=0.013),中位生存期显著延长(30.9个月和21.0个月,P=0.013)。此外,对于接受肝转移切除的A组患者,其中位生存时间较未手术者显著延长(46.4个月和25.7个月,P<0.01)。结论对于首诊无法切除的KRAS野生型CLM患者,与单纯化疗相比,西妥昔单抗联合化疗可提高患者肝转移手术切除率,提高缓解率并改善总生存。
Background and Objective The liver is the most common distant metastasis of colorectal cancer. Approximately half of patients with colon cancer will develop liver metastases in the course of the disease. In the past, most clinical studies focused on the targeted drug cetuximab were usually only concerned with the impact of KRAS mutation status on the treatment and the efficacy of the combination with various chemotherapy regimens. Few studies have explored whether it is helpful to improve the secondary resection of liver metastases Conversion rate. Therefore, this study evaluated the efficacy of cetuximab plus chemotherapy in first-line treatment of radical liver resection for unresectable patients with simultaneous simplex liver metastases (KRM) of KRAS wild-type colon cancer and to assess tumor response and Total patient survival. Subjects and Methods KRAS wild-type patients with concurrent colorectal cancer who were unresectable and limited hepatic metastases were randomized to receive chemotherapy with FOLFIRI (fluorouracil, leucovorin and irinotecan) or mFOLFOX6 (modified Fluorouracil, leucovorin and oxaliplatin) combined with cetuximab (group A) or chemotherapy alone (group B). The primary endpoint of the study was the rate of surgical resection of liver metastases after treatment. Secondary endpoints were objective response rates and survival rates. A total of 138 patients were enrolled in the intention-to-treat population; 70 of them were randomized to Group A and 68 were assigned to Group B. The median follow-up time was 25.0 months, and the 3-year overall survival (OS) and median survival time (MST) for all patients were 30% and 24.4 months. The resection rate of R0 was 25.7% (18/70) in group A and 7.4% (5/68) in group B, and the difference was statistically significant (P <0.01). Among the 18 patients undergoing hepatectomy, there were 6 cycles (4 ~ 12 cycles) of preoperative chemotherapy. Among them, 11 had multiple hepatectomy, 4 had right hemihepatectomy, and 3 had left hemihepatectomy. No serious complications after surgery. The objective response rate and 3-year OS rate were significantly higher in group A than in group B (57.1% vs 29.4%, P <0.01; 41% vs 18%, P = 0.013, respectively) (30.9 months and 21.0 months, P = 0.013). In addition, patients in group A who underwent hepatic metastases had a significantly longer median survival than those who did not (46.4 and 25.7 months, P <0.01). Conclusions Cetuximab in combination with chemotherapy increases the surgical resection rate, improves response rate, and improves overall survival in patients with clinically unresectable KRAS wild-type CLM compared with chemotherapy alone.