派姆单抗
帕博利珠单抗 (pembrolizumab) 是一种抗程序性细胞死亡蛋白 1 (抗 PD1) 抗体检查点抑制剂。它通过阻断引起肿瘤耐药性的通路而发挥作用。[98]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;8(35):59901-14.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601788/http://www.ncbi.nlm.nih.gov/pubmed/28938692?tool=bestpractice.com 帕博利珠单抗 (pembrolizumab) 已获得美国食品药品监督管理局 (FDA) 的加速批准，用于治疗存在以下情况的患者：有不可切除或转移性实体肿瘤，并且存在微卫星不稳定性高或错配修复缺陷的生物标记物。[99]US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. May 2017 [internet publication].https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm 这种批准是独一无二的，即：FDA 首次批准一种癌症治疗方法是基于肿瘤生物标志物的存在而非肿瘤在体内的位置。 目前，研究派姆单抗治疗胰腺癌效果的 1 期和 2 期试验正在进行中。[100]ClinicalTrials.gov. A phase IIb pilot study to assess the efficacy, safety and pharmacodynamic effects of pembrolizumab and BL-8040 in patients with metastatic pancreatic cancer. April 2018 [internet publication].https://clinicaltrials.gov/ct2/show/NCT02907099[101]ClinicalTrials.gov. Phase Ib trial of pembrolizumab and XL888 in patients with advanced gastrointestinal malignancies. April 2018 [internet publication].https://clinicaltrials.gov/ct2/show/NCT03095781[102]ClinicalTrials.gov. A randomized multicenter phase Ib/II study to assess the safety and the immunological effect of chemoradiation therapy (CRT) in combination with pembrolizumab (MK-3475) compared to CRT alone in patients with resectable or borderline resectable pancreatic cancer. September 2017 [internet publication].https://clinicaltrials.gov/ct2/show/NCT02305186
临床试验
对于临床各期胰腺癌均有多项临床研究正在进行。National Cancer Institute: clinical trials 研究已显著增加了我们在分子水平上对胰腺癌性质的了解：瞄准特定通路或密集促结缔组织增生间质的特定药物是受到极大关注的领域，也是临床试验的重要关注点。 对于未筛选的胰腺癌患者，初始的临床试验结果对预后的改善令人失望。以后的研究重点依然是新型靶向药物，联合治疗方案（靶向药及细胞毒性药物）的研究及特定患者的筛选。[103]Wong HH, Lemoine NR. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat Rev Gastroenterol Hepatol. 2009 Jul;6(7):412-22.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882232/http://www.ncbi.nlm.nih.gov/pubmed/19506583?tool=bestpractice.com[104]Kindler HL, Niedzwiecki D, Hollis D, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010 Aug 1;28(22):3617-22.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917317/http://www.ncbi.nlm.nih.gov/pubmed/20606091?tool=bestpractice.com[105]Moinpour CM, Vaught NL, Goldman B, et al. Pain and emotional well-being outcomes in Southwest Oncology Group-directed intergroup trial S0205: a phase III study comparing gemcitabine plus cetuximab versus gemcitabine as first-line therapy in patients with advanced pancreas cancer. J Clin Oncol. 2010 Aug 1;28(22):3611-6.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917316/http://www.ncbi.nlm.nih.gov/pubmed/20606094?tool=bestpractice.com[106]Philip PA, Benedetti J, Corless CL, et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605-10.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917315/http://www.ncbi.nlm.nih.gov/pubmed/20606093?tool=bestpractice.com[107]Eltawil KM, Renfrew PD, Molinari M. Meta-analysis of phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer. HPB (Oxford). 2012 Apr;14(4):260-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371213/http://www.ncbi.nlm.nih.gov/pubmed/22404265?tool=bestpractice.com[108]Löhr JM, Haas SL, Bechstein WO, et al. Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial. Ann Oncol. 2012 May;23(5):1214-22.https://academic.oup.com/annonc/article/23/5/1214/192410http://www.ncbi.nlm.nih.gov/pubmed/21896540?tool=bestpractice.com[109]Chang DK, Grimmond SM, Biankin AV. Pancreatic cancer genomics. Curr Opin Genet Dev. 2014 Feb;24:74-81.http://www.ncbi.nlm.nih.gov/pubmed/24480245?tool=bestpractice.com[110]Borad MJ, Reddy SG, Bahary N, et al. Randomized phase II trial of gemcitabine plus TH-302 versus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2015 May 1;33(13):1475-81.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881365/http://www.ncbi.nlm.nih.gov/pubmed/25512461?tool=bestpractice.com[111]Ko AH, Tempero MA, Shan YS, et al. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013 Aug 20;109(4):920-5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749576/http://www.ncbi.nlm.nih.gov/pubmed/23880820?tool=bestpractice.com
替加氟/吉美嘧啶/奥替拉西 (S-1)
与吉西他滨单药治疗相比，使用 S-1 的辅助化疗提高了日本已切除胰腺癌患者的 5 年总生存期。[112]Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57.http://www.ncbi.nlm.nih.gov/pubmed/27265347?tool=bestpractice.com 替加氟是氟尿嘧啶的前体药物。 这种复方药物已获准在日本使用，但尚未获准在其他国家/地区使用。
