Uetake Hiroyuki, Yasuno Masamichi, Ishiguro Megumi, Kameoka Shingo, Shimada Yasuhiro, Takahashi Keiichi, Watanabe Toshiaki, Muro Kei, Baba Hideo, Yamamoto Junji, Mizunuma Nobuyuki, Tamagawa Hiroshi, Mochizuki Izumi, Kinugasa Yusuke, Kikuchi Takashi, Sugihara Kenichi
Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan,
Ann Surg Oncol. 2015 Mar;22(3):908-15. doi: 10.1245/s10434-014-4094-7. Epub 2014 Dec 3.
A phase II clinical trial was conducted on colorectal cancer patients with only liver metastases (focal diameter exceeds 5 cm or the number of liver metastases is ≥5; H2·H3) to evaluate the liver resection rate and safety after 6 cycles of mFOLFOX6+bevacizumab (BV) therapy.
mFOLFOX6+BV therapy was applied for 6 cycles to the patients with H2·H3 liver only metastasis. Hepatectomy was considered after the sixth cycle as a rule, and was performed if possible. The primary endpoint was the curative hepatectomy rate (R0 resection rate).
Forty-six patients were registered and 45 patients were included in the efficacy analysis. Of the 19 patients rated as unresectable before therapy, 18 completed 6 cycles of mFOLFOX6+BV therapy and subsequently underwent hepatectomy (16 were R0-resected). Of the 26 initially unresectable patients, 6 underwent hepatectomy (4 were RO-resected). The overall R0 resection rate was 44.4% (20/45). Chemotherapy-associated grade 3 or higher adverse events included neutrophil decreased (17.4%) and leukocyte decreased (8.7%), fatigue (6.5%) etc. Only hypertension (6.5%) and venous thromboembolism (2.2%) were BV-associated grade 3 or higher adverse events. Among the 25 patients who underwent hepatectomy, intraoperative/postoperative complications included grade 3 wound infections (2 cases), biloma, delayed wound healing and intraperitoneal abscess (each 1 case).
In colorectal cancer patients with liver-only metastases, mFOLFOX6+ BV therapy yielded a high hepatectomy rate and a high percentage of initially unresectable and subsequently resectable cases. The chemotherapy associated adverse events and hepatectomy complications were both within acceptable ranges.
对仅发生肝转移（病灶直径超过5 cm或肝转移灶数量≥5；H2·H3）的结直肠癌患者进行了一项II期临床试验，以评估mFOLFOX6+贝伐单抗（BV）治疗6个周期后的肝切除率和安全性。
对H2·H3期仅肝转移的患者应用mFOLFOX6+BV治疗6个周期。通常在第六个周期后考虑进行肝切除术，如有可能则进行手术。主要终点是根治性肝切除率（R0切除率）。
登记了46例患者，45例患者纳入疗效分析。在治疗前被评为不可切除的19例患者中，18例完成了6个周期的mFOLFOX6+BV治疗，随后接受了肝切除术（16例为R0切除）。在最初26例不可切除的患者中，6例接受了肝切除术（4例为R0切除）。总体R0切除率为44.4%（20/45）。化疗相关的3级或更高等级不良事件包括中性粒细胞减少（17.4%）、白细胞减少（8.7%）、疲劳（6.5%）等。仅高血压（6.5%）和静脉血栓栓塞（2.2%）是与BV相关的3级或更高等级不良事件。在接受肝切除术的25例患者中，术中和术后并发症包括3级伤口感染（2例）、胆漏、伤口愈合延迟和腹腔脓肿（各1例）。
在仅发生肝转移的结直肠癌患者中，mFOLFOX6+BV治疗产生了较高的肝切除率，以及较高比例的最初不可切除但随后可切除的病例。化疗相关不良事件和肝切除术后并发症均在可接受范围内。
