A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only

Oncologist. 2016 Mar;21(3):279-80. doi: 10.1634/theoncologist.2015-0439. Epub 2016 Feb 24.


Background: Patients with liver-only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first-line treatment for KRAS wild-type mCRC with liver-only metastasis.

Methods: Patients received FOLFOXIRI (5-FU, 3,200 mg/m(2), 48-hour continuous intravenous (i.v.) infusion; leucovorin, 200 mg/m(2) i.v.; irinotecan, 125 mg/m(2); oxaliplatin, 85 mg/m(2) i.v.) and panitumumab (6 mg/kg i.v.) on day 1 of 14-day cycles. Patients were restaged and evaluated for surgery every four cycles. Planned enrollment was originally 49 patients. The primary endpoint was objective response rate.

Results: Fifteen patients (median age: 55 years; 87% male) received a median 6 cycles of treatment (range: 1-33 cycles); 10 patients (67%) were surgical candidates at baseline. Twelve patients were evaluable for clinical response; 9 (60%) achieved partial response. Ten patients underwent surgery; all were complete resections and pathologic partial response. Treatment-related grade 3 adverse events included diarrhea (33%) and rash (20%). Enrollment was halted because of emerging data on expanded KRAS/NRAS mutations beyond the region we initially examined, and the potential for negative interaction with oxaliplatin-based therapy. Eight patients underwent expanded KRAS/NRAS analysis outside exon 2; no additional mutations were found.

Conclusion: KRAS/NRAS mutations outside the region tested in this study were recently shown to be associated with inferior survival on similar treatment regimens. Therefore, this trial was stopped early. This regimen remains a viable option for patients with liver-only mCRC in the KRAS/NRAS wild-type population. Enrollment criteria on future studies should include testing for the newly identified mutations.


• 该方案对仅有肝转移的结直肠癌患者而言是可行的选择。

• 未来研究的入选标准应包括对近期才发现的 KRAS 突变进行检测。


背景. 对于仅有肝转移且无法行根治性切除术的结直肠癌 (mCRC) 患者, 未来可能在接受更为积极的化疗方案治疗后变得可以手术切除。我们在本项非随机临床试验中对亚叶酸钙、5-氟尿嘧啶 (5-FU)、奥沙利铂和伊立替康 (FOLFOXIRI) 联合表皮生长因子受体 (EGFR) 抑制剂帕尼单抗用于一线治疗仅有肝转移的 KRAS 野生型 mCRC 患者进行了评价。

方法. 患者接受 FOLFOXIRI [5-FU 3 200 mg/m2持续静注 (IV) 48 小时, 亚叶酸钙 200 mg/m2 IV, 伊立替康 125 mg/m2, 奥沙利铂 85 mg/m2 IV]以及帕尼单抗 (6 mg/kg IV), 第 1 天给药, 14 天为一周期。每 4 个周期对患者进行重新分期, 并评价手术的可能性。最初计划招募 49 例患者。主要终点为客观缓解率。

结果. 15 例患者 (中位年龄 55 岁, 87%为男性) 接受了中位 6 周期治疗 (范围: 1∼33 周期); 10 例患者 (67%) 在基线时可以行手术。12 例患者临床治疗反应可评价; 9例 (60%) 患者达到部分缓解。10 例患者接受了手术, 均完整切除且达到病理学部分缓解。治疗相关性 3 级不良事件包括腹泻 (33%) 和皮疹 (20%)。因新出现的扩展 KRAS/NRAS 突变数据超出了我们最初检测的区域, 并且可能与以奥沙利铂为基础的方案有潜在的不良交互作用, 因此我们停止了招募。8 例患者接受了除外显子 2 以外的扩展 KRAS/NRAS 分析, 未发现其他突变。

结论. 最近研究显示, 本研究检验区域以外的KRAS/NRAS突变与和本研究相似的治疗方案生存转归较差相关。因此本研究提前停止了。但是对于仅有肝转移的KRAS/NRAS野生型mCRC患者人群, 我们的方案仍然是可行的治疗方案。未来研究的入选标准应包括对新发现的突变进行检测。The Oncologist 2016;21:279–280d

Trial registration: ClinicalTrials.gov NCT01226719.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Panitumumab
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Treatment Outcome


  • Antibodies, Monoclonal
  • KRAS protein, human
  • Organoplatinum Compounds
  • Panitumumab
  • Proto-Oncogene Proteins p21(ras)
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • FOLFOXIRI protocol

Associated data

  • ClinicalTrials.gov/NCT01226719