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前瞻性 II 期研究:新辅助 FOLFOX6 加西妥昔单抗治疗结直肠癌和不可切除的肝转移患者。

Prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver-only metastasis.

机构信息

Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.

出版信息

Cancer Chemother Pharmacol. 2013 Jul;72(1):223-30. doi: 10.1007/s00280-013-2190-1. Epub 2013 May 21.


DOI:10.1007/s00280-013-2190-1
PMID:23689915
Abstract

PURPOSE: Liver resection may offer the only chance of cure in patients with colorectal cancer with liver metastases. In the unresectable cases, neoadjuvant chemotherapy could render curability if resectability could be achieved. METHODS: Newly diagnosed K-RAS wild-type colorectal cancer patients with unresectable liver-only metastases were treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) plus cetuximab every 2 weeks for a maximum of 12 cycles. Clinical response was evaluated every 6 weeks, and surgery was performed at the physician's discretion in patients with sufficient tumor shrinkage, followed by chemotherapy with the same regimen, to complete a total of 12 cycles. The primary endpoint was an overall R0 resection rate. RESULTS: Between July 2008 and December 2009, 73 patients were registered from 11 Korean centers. Among 53 (73 %) patients who showed at least partial response, surgery with curative intent was attempted in 36 (49 %) patients. Intention-to-treat analysis revealed a R0 resection rate of 27 % (20/73) including 8 patients whose unresectable liver metastases were successfully treated with radiofrequency ablation (RFA). The most common grade 3 and 4 toxicity was neutropenia (50/462 cycles, 10.7 %). Median time to progression (TTP) was 9.8 months (range 0.5-31.8) in all patients, but we observed TTP of 14.1 months (range 1.3 to -30.8) in patients who received R0 resection and RFA + R0 resection. CONCLUSIONS: Neoadjuvant chemotherapy with FOLFOX6 plus cetuximab showed high response rates and increased the resectability in colorectal patients with non-resectable liver-only metastases.

摘要

目的:对于结直肠癌伴肝转移患者,肝切除术可能是唯一的治愈机会。对于不可切除的病例,如果能够达到可切除性,则新辅助化疗可能会提高治愈能力。

方法:对新诊断的 K-RAS 野生型结直肠癌伴不可切除的肝转移患者,采用氟尿嘧啶、亚叶酸钙和奥沙利铂(FOLFOX6)联合西妥昔单抗每 2 周治疗 1 次,最多 12 个周期。每 6 周评估一次临床反应,在有足够肿瘤缩小的患者中由医生决定进行手术,然后用相同方案进行化疗,总共完成 12 个周期。主要终点是总体 R0 切除率。

结果:2008 年 7 月至 2009 年 12 月,来自 11 个韩国中心的 73 名患者登记入组。在 53 名(73%)至少有部分缓解的患者中,36 名(49%)有治愈意图的患者尝试了手术。意向治疗分析显示 R0 切除率为 27%(20/73),其中 8 名无法切除的肝转移灶成功接受了射频消融(RFA)治疗。最常见的 3 级和 4 级毒性是中性粒细胞减少(50/462 个周期,10.7%)。所有患者的中位无进展生存期(TTP)为 9.8 个月(范围 0.5-31.8),但我们观察到接受 R0 切除和 RFA+R0 切除的患者 TTP 为 14.1 个月(范围 1.3 至-30.8)。

结论:FOLFOX6 联合西妥昔单抗的新辅助化疗显示出高反应率,并提高了结直肠癌伴不可切除的肝转移患者的可切除性。

相似文献

[1]
Prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver-only metastasis.

Cancer Chemother Pharmacol. 2013-5-21

[2]
Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.

Lancet Oncol. 2009-11-26

[3]
A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer.

Clin Colorectal Cancer. 2010-4

[4]
Neoadjuvant treatment with weekly high-dose 5-fluorouracil as a 24h-infusion, folinic acid and biweekly oxaliplatin in patients with primary resectable liver metastases of colorectal cancer: long-term results of a phase II trial.

Med Sci Monit. 2010-2

[5]
Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

PLoS Med. 2024-5

[6]
Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases.

J Clin Oncol. 2013-4-8

[7]
Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for patients with unresectable liver-only metastases from colorectal cancer in Japan: ROOF study.

Int J Clin Oncol. 2012-3-2

[8]
Liver resection rate following downsizing chemotherapy with cetuximab in metastatic colorectal cancer: UK retrospective observational study.

Eur J Surg Oncol. 2015-4

[9]
A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial.

Br J Cancer. 2012-11-20

[10]
Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-ras status for unresectable colorectal liver metastasis (BECK study).

J Hepatobiliary Pancreat Sci. 2015-8

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[7]
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[8]
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[9]
Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial.

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[10]
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