三氟尿苷/替吡嘧啶 (Trifluridine/tipiracil)
三氟尿苷/替吡嘧啶（也称为 TAS-102）是一种含三氟尿苷的口服复方药物，是一种基于胸苷的核酸类似物，可作为药物的细胞毒性成分，而替吡嘧啶是一种胸苷磷酸化酶抑制剂，可阻止三氟尿苷的快速分解。在一项随机、安慰剂对照的 III 期临床试验中，对于在采用至少两种既往化疗方案治疗期间出现疾病进展的患者，三氟尿苷/替吡嘧啶可使总生存期延长 1.6 个月。[197]Mayer RJ, Van Cutsem E, Falcone A, et al.; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372:1909-1919.http://www.nejm.org/doi/full/10.1056/NEJMoa1414325#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/25970050?tool=bestpractice.com 这使得三氟尿苷/替吡嘧啶获批用于接受过氟嘧啶、奥沙利铂、伊立替康、至少一种 VEGF 抑制剂和一种 EGFR 抑制剂（RAS 野生型）治疗的转移性结直肠癌患者。
放射性标记的微球
空心球体通常由填充有钇-90 的生物可降解蛋白质制成，用于介入放射学手术（即选择性体内放射治疗或放射栓塞术），将高剂量辐射直接靶向瞄准不可切除的肝转移。五项关于结直肠癌的研究结果之间存在矛盾。虽然有些研究显示此疗法可产生无进展生存获益和总体生存获益，但其他研究表明该疗法并未改善疾病进展或总生存期。[198]Townsend AR, Chong LC, Karapetis C, et al. Selective internal radiation therapy for liver metastases from colorectal cancer. Cancer Treat Rev. 2016;50:148-154.http://www.ncbi.nlm.nih.gov/pubmed/27690234?tool=bestpractice.com[199]van Hazel GA, Heinemann V, Sharma NK, et al. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;34:1723-1731.http://ascopubs.org/doi/full/10.1200/JCO.2015.66.1181http://www.ncbi.nlm.nih.gov/pubmed/26903575?tool=bestpractice.com[200]Van Hazel G, Blackwell A, Anderson J, et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88:78-85.http://www.ncbi.nlm.nih.gov/pubmed/15499601?tool=bestpractice.com[201]Gray B, Van Hazel G, Hope M, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. 2001;12:1711-1720.http://www.ncbi.nlm.nih.gov/pubmed/11843249?tool=bestpractice.com[202]Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010;28:3687-3694.http://ascopubs.org/doi/full/10.1200/JCO.2010.28.5643http://www.ncbi.nlm.nih.gov/pubmed/20567019?tool=bestpractice.com 有关结直肠癌的更多临床试验正在进行中。[198]Townsend AR, Chong LC, Karapetis C, et al. Selective internal radiation therapy for liver metastases from colorectal cancer. Cancer Treat Rev. 2016;50:148-154.http://www.ncbi.nlm.nih.gov/pubmed/27690234?tool=bestpractice.com
抗 PD1 检查点抑制剂
派姆单抗 (pembrolizumab) 和尼沃鲁单抗 (nivolumab) 是两种抗 PD1 抗体检查点抑制剂。二者通过阻断引起肿瘤耐药性的通路而发挥作用。[203]Wang X, Bao Z, Zhang X, et al. Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis. Oncotarget. 2017 May 31 [Epub ahead of print].http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=18316&pubmed-linkout=1http://www.ncbi.nlm.nih.gov/pubmed/28614783?tool=bestpractice.com 派姆单抗和尼沃鲁单抗已获得美国食品药品监督管理局 (Food and Drug Administration, FDA) 的加速批准，用于治疗可切除性或转移性实体瘤患者，这些实体瘤存在一种被称为微卫星不稳定性高 (microsatellite instability-high, MSI-H) 或错配修复缺陷 (mismatch repair deficient, dMMR) 的生物标志物。[204]US Food and Drug Administration. FDA approves first cancer treatment for any solid tumor with a specific genetic feature. May 2017. https://www.fda.gov/ (last accessed 18 July 2017).https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm 这些批准是独一无二的，因为这是 FDA 首次批准两种基于肿瘤生物标志物（而非基于肿瘤在体内的位置）的癌症治疗方法。目前，研究派姆单抗和尼沃鲁单抗治疗结直肠癌疗效的Ⅰ期和 Ⅱ 期临床试验正在进行中。[205]ClinicalTrials.gov. Study of pembrolizumab in combination with chemotherapy for patients with advanced colorectal cancer. March 2017. https://clinicaltrials.gov/ (last accessed 18 July 2017).https://clinicaltrials.gov/ct2/show/NCT02375672[206]ClinicalTrials.gov. Epacadostat in combination with pembrolizumab and azacitidine in subjects with metastatic colorectal cancer. June 2017. https://clinicaltrials.gov/ (last accessed 18 July 2017).https://clinicaltrials.gov/ct2/show/NCT03182894[207]ClinicalTrials.gov. Assess the efficacy of pembrolizumab plus radiotherapy or ablation in metastatic colorectal cancer patients. June 2017. https://clinicaltrials.gov/ (last accessed 18 July 2017).https://clinicaltrials.gov/ct2/show/NCT02437071[208]ClinicalTrials.gov. A study evaluating TAS-102 plus nivolumab in patients with MSS CRC. July 2017. https://clinicaltrials.gov/ (last accessed 17 August 2017).https://clinicaltrials.gov/ct2/show/NCT02860546[209]ClinicalTrials.gov. Study of S 95005 in combination with oxaliplatin in metastatic colorectal cancer. April 2017. https://clinicaltrials.gov/ (last accessed 17 August 2017).https://clinicaltrials.gov/ct2/show/NCT02848443
