胰腺癌

手术切除是可切除疾病患者的首选治疗方式。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85

手术的性质和范围取决于肿瘤的位置和部位。

当肿瘤位于胰头时最常用的手术方式是切除胃窦（Kausch-Whipple's)或保留幽门(Traverso-Longmire's)胰十二指肠切除术。

保留幽门的胰十二指肠切除术和Kausch-Whipple胰十二指肠切除术后的生存质量和生存率可能相同。[50]Hüttner FJ, Fitzmaurice C, Schwarzer G, et al. Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma. Cochrane Database Syst Rev. 2016 Feb 16;(2):CD006053.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006053.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26905229?tool=bestpractice.com[87]Vickers MM, Powell ED, Asmis TR, et al. Comorbidity, age and overall survival in patients with advanced pancreatic cancer - results from NCIC CTG PA.3: a phase III trial of gemcitabine plus erlotinib or placebo. Eur J Cancer. 2012 Jul;48(10):1434-42.http://www.ncbi.nlm.nih.gov/pubmed/22119354?tool=bestpractice.com [ ]How do pylorus-preserving and classic pancreaticoduodenectomy compare in people undergoing surgical treatment of periampullary and pancreatic carcinoma?https://cochranelibrary.com/cca/doi/10.1002/cca.1321/full显示答案

相比标准清扫术式，淋巴结扩大清扫不仅没有提高生存率，反而增加并发症发生的风险。[52]Iqbal N, Lovegrove RE, Tilney HS, et al. A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: a meta-analysis of 1909 patients. Eur J Surg Oncol. 2009 Jan;35(1):79-86.http://www.ncbi.nlm.nih.gov/pubmed/18356005?tool=bestpractice.com

针对经选择患者组全部患者的治疗推荐

在所有的胰腺癌患者中， “胰酶替代治疗应该与饮食和额外营养补充一起保持患者体重以及提高生存质量。[11]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955499/http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com

高级别证据表明黄疸患者术前常规置入支架在手术效果中并没有获益，反而增加了感染性并发症。[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com[56]van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010 Jan 14;362(2):129-37.http://www.nejm.org/doi/full/10.1056/NEJMoa0903230#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/20071702?tool=bestpractice.com

然而有胆管炎症状的患者（理论上至少要把手术时间推迟10天）可能需要放入胆管支架， 如果术前需要放入支架，塑料性支架可在内镜下放入。[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com

临床试验研究表明术前接受新辅助治疗的患者推荐使用临时性的胆管支架。

胰腺癌的新辅助治疗（术前给予治疗以减小肿瘤大小和范围，从而提高手术完整切除肿瘤组织的成功率）目前仍在研究中，尚未发布任何大型随机对照试验。

新辅助联合化疗或基于氟尿嘧啶的放化疗可提供给以下几类患者：临床怀疑有肿瘤转移（但无放射学证据）的患者；有临界体力状态但可通过全身性治疗得到改善的患者。 然而，没有生存率显著提高的报道。[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com[57]Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012 May;19(5):1644-62.http://www.ncbi.nlm.nih.gov/pubmed/22012027?tool=bestpractice.com[58]Gillen S, Schuster T, Meyer Zum Büschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010 Apr 20;7(4):e1000267.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857873/http://www.ncbi.nlm.nih.gov/pubmed/20422030?tool=bestpractice.com[59]Morganti AG, Massaccesi M, La Torre G, et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 2010 Jan;17(1):194-205.http://www.ncbi.nlm.nih.gov/pubmed/19856029?tool=bestpractice.com

从技术上讲不可切除的肿瘤很少能通过新辅助疗法得到切除。[60]Khorana AA, Mangu PB, Berlin J, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017 Jul 10;35(20):2324-8.http://ascopubs.org/doi/full/10.1200/JCO.2017.72.4948http://www.ncbi.nlm.nih.gov/pubmed/28398845?tool=bestpractice.com

目前正在进行测试基于吉西他滨的联合化疗、FOLFIRINOX（亚叶酸、氟尿嘧啶、伊立替康和奥沙利铂）以及放化疗等不同的新辅助治疗方案的前瞻性随机对照试验（如 ESPAC-5 或 NEOPAC）。

有关方案和剂量指南，请参见本地专科医师方案。

针对经选择患者组全部患者的治疗推荐

辅助治疗是指在手术切除术后为减少复发风险而采用的治疗手段。 对于未接受新辅助疗法但已切除胰腺癌的患者，应给予 6 个月的辅助化疗。[60]Khorana AA, Mangu PB, Berlin J, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017 Jul 10;35(20):2324-8.http://ascopubs.org/doi/full/10.1200/JCO.2017.72.4948http://www.ncbi.nlm.nih.gov/pubmed/28398845?tool=bestpractice.com

美国临床肿瘤学会 (American Society of Clinical Oncology, ASCO) 和英国国家卫生与临床优化研究所建议，在无需担心毒性或耐受性的情况下，可使用辅助性吉西他滨和卡培他滨双联方案。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85[60]Khorana AA, Mangu PB, Berlin J, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017 Jul 10;35(20):2324-8.http://ascopubs.org/doi/full/10.1200/JCO.2017.72.4948http://www.ncbi.nlm.nih.gov/pubmed/28398845?tool=bestpractice.com ASCO 指南基于一项纳入 732 例切除胰腺导管腺癌 (ESPAC-4) 患者的多中心、开放性随机试验。 该研究发现，与使用吉西他滨单药治疗相比，使用卡培他滨加吉西他滨的辅助疗法显著延长了生存期（28.0 个月 vs 25.5 个月）。[61]Neoptolemos JP, Palmer D, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol. 2016;34 (Suppl 15):LBA4006.http://meetinglibrary.asco.org/record/122648/abstract 如果这种联合治疗存在禁忌，ASCO 推荐吉西他滨单药治疗或氟尿嘧啶加亚叶酸。 亚叶酸可增强氟尿嘧啶的效果，因此常与后者联合使用。 吉西他滨和氟尿嘧啶均可抑制胸苷酸合成酶，这是合成胸苷所必需的酶。

参考当地专科医生治疗方案作为剂量指导。

针对经选择患者组全部患者的治疗推荐

关于辅助放化疗是否适合用于未完全切除的癌症患者，目前仍有争议。ESPAC-1 及 Meta 分析的数据[62]Stocken DD, Büchler MW, Dervenis C, et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005 Apr 25;92(8):1372-81.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361989/http://www.ncbi.nlm.nih.gov/pubmed/15812554?tool=bestpractice.com[63]Butturini G, Stocken DD, Wente MN, et al; Pancreatic Cancer Meta-Analysis Group. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg. 2008 Jan;143(1):75-83.http://jamanetwork.com/journals/jamasurgery/fullarticle/401321http://www.ncbi.nlm.nih.gov/pubmed/18209156?tool=bestpractice.com证据 B腺癌切缘阳性患者的生存率：中级别证据表明化疗是一项有效的辅助治疗，效果优于同步放化疗， 有试验表明胰腺癌切缘阳性的患者接受化疗后，2年和5年生存率要比未接受化疗者高。[62]Stocken DD, Büchler MW, Dervenis C, et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005 Apr 25;92(8):1372-81.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361989/http://www.ncbi.nlm.nih.gov/pubmed/15812554?tool=bestpractice.com受试者＜200名的随机对照临床试验（RCT）、受试者＞200名且方法学存在缺陷的随机对照临床试验（RCT）、方法学存在缺陷的系统评价或者高质量的观察性（队列）研究。 表明放化疗似乎只有在肿瘤不完全切除（R1 或 R2 切除）的情况下才能延长生存时间。若选择放化疗做辅助治疗，推荐以氟尿嘧啶为基础的放化疗联合全身性应用吉西他滨。[64]Picozzi VJ, Pisters PW, Vickers SM, et al. Strength of the evidence: adjuvant therapy for resected pancreatic cancer. J Gastrointest Surg. 2008 Apr;12(4):657-61.http://www.ncbi.nlm.nih.gov/pubmed/18157582?tool=bestpractice.com[65]Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26.http://jamanetwork.com/journals/jama/fullarticle/181567http://www.ncbi.nlm.nih.gov/pubmed/18319412?tool=bestpractice.com[66]Regine WF, Winter KA, Abrams R, et al. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548408/http://www.ncbi.nlm.nih.gov/pubmed/21499862?tool=bestpractice.com

应仅考虑对已完全从手术中恢复的患者进行辅助化疗或放化疗。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85 治疗最好在手术过后的 4-8 周内开始。 不过，辅助化疗时机相关数据表明，只要完成 6 个周期的辅助化疗，术后治疗延迟 12 周不会对临床结局产生不利影响。[67]Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014 Feb 20;32(6):504-12.http://ascopubs.org/doi/full/10.1200/jco.2013.50.7657http://www.ncbi.nlm.nih.gov/pubmed/24419109?tool=bestpractice.com

不得对已接受新辅助放疗或放化疗的患者进行辅助放化疗。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85[60]Khorana AA, Mangu PB, Berlin J, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017 Jul 10;35(20):2324-8.http://ascopubs.org/doi/full/10.1200/JCO.2017.72.4948http://www.ncbi.nlm.nih.gov/pubmed/28398845?tool=bestpractice.com

参考当地专科医生治疗方案作为剂量指导。

内镜下治疗优于手术方式。

然而切除失败的患者（尝试切除局部晚期肿瘤）可能从旁路手术获益，解决胆管和胃通道的梗阻，谓之双旁路途径，胆管旁路在胆汁经旁路引流中优于胆囊旁路，[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com 或者可能获益于预防性胃肠吻合术。[70]Huser N, Michalski CW, Schuster T, et al. Systematic review and meta-analysis of prophylactic gastroenterostomy for unresectable advanced pancreatic cancer. Br J Surg. 2009 Jul;96(7):711-9.http://www.ncbi.nlm.nih.gov/pubmed/19526616?tool=bestpractice.com

内镜支架置入术优于经肝塑料支架置入。[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com

根据临床因素、部位的可行性还有专业经验来选择塑料型支架还是自膨胀金属支架。

塑料型支架寿命是3个月，如果患者一般状况较好、预后良好的话推荐使用金属支架。[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com证据 A不可切除性胰腺癌引起的梗阻性黄疸症状的缓解：高级别证据表明内镜下金属支架置入可解决胰腺癌引起的梗阻性黄疸。[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com系统评价或者受试者＞200名的随机对照临床试验（RCT）。

针对经选择患者组全部患者的治疗推荐

当解除胆道梗阻及（如有需要）胃梗阻后，进行全身性治疗结合联合化疗或放化疗控制肿瘤。

体力状态良好的患者似乎可从基于吉西他滨并联合铂类似物（奥沙利铂或顺铂）或氟嘧啶（氟尿嘧啶或卡培他滨）的联合化疗中获益。[2]Klimstra DS, Pitman MB, Hruban RH. An algorithmic approach to the diagnosis of pancreatic neoplasms. Arch Pathol Lab Med. 2009 Mar;133(3):454-64.http://www.archivesofpathology.org/doi/10.1043/1543-2165-133.3.454http://www.ncbi.nlm.nih.gov/pubmed/19260750?tool=bestpractice.com[73]Sultana A, Tudur Smith C, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses. Br J Cancer. 2008 Jul 8;99(1):6-13.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453014/http://www.ncbi.nlm.nih.gov/pubmed/18577990?tool=bestpractice.com[74]Sultana A, Smith CT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2007 Jun 20;25(18):2607-15.http://ascopubs.org/doi/full/10.1200/JCO.2006.09.2551http://www.ncbi.nlm.nih.gov/pubmed/17577041?tool=bestpractice.com[75]Sultana A, Ghaneh P, Cunningham D, et al. Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison. BMC Cancer. 2008 Jul 8;8:192.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474853/http://www.ncbi.nlm.nih.gov/pubmed/18611273?tool=bestpractice.com[76]Poplin E, Feng Y, Berlin J, et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727286/http://www.ncbi.nlm.nih.gov/pubmed/19581537?tool=bestpractice.com[77]Heinemann V, Labianca R, Hinke A, et al. Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study. Ann Oncol. 2007 Oct;18(10):1652-9.https://academic.oup.com/annonc/article/18/10/1652/133336http://www.ncbi.nlm.nih.gov/pubmed/17660491?tool=bestpractice.com[78]Heinemann V, Boeck S, Hinke A, et al. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer. 2008 Mar 28;8:82.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292732/http://www.ncbi.nlm.nih.gov/pubmed/18373843?tool=bestpractice.com[79]Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8.http://ascopubs.org/doi/full/10.1200/JCO.2009.24.2446http://www.ncbi.nlm.nih.gov/pubmed/19858379?tool=bestpractice.com [ ]How do gemcitabine‐containing dual chemotherapy regimens compare with gemcitabine alone for people with advanced pancreatic cancer?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2216/full显示答案是否应加用厄洛替尼（erlotini，一种口服人表皮生长因子受体 1 (HER1)/表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂）仍存在争议。初步研究显示了有限但显著的生存获益（2 周），但当局部晚期胰腺癌患者被随机分配接受吉西他滨或吉西他滨联合厄洛替尼治疗时，未见到总生存期的显著差异。[80]Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6.http://ascopubs.org/doi/full/10.1200/JCO.2006.07.9525http://www.ncbi.nlm.nih.gov/pubmed/17452677?tool=bestpractice.com[81]Heinemann V, Vehling-Kaiser U, Waldschmidt D, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9.http://www.ncbi.nlm.nih.gov/pubmed/22773551?tool=bestpractice.com[82]Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53.http://www.ncbi.nlm.nih.gov/pubmed/27139057?tool=bestpractice.com

在有转移性疾病的情况下，FOLFIRINOX 治疗方案（亚叶酸、氟尿嘧啶、伊立替康和奥沙利铂）或吉西他滨联合纳米微粒白蛋白结合型紫杉醇治疗是合适的替代方案。[36]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site[83]Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631139/http://www.ncbi.nlm.nih.gov/pubmed/24131140?tool=bestpractice.com[84]Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.http://www.nejm.org/doi/full/10.1056/NEJMoa1011923#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/21561347?tool=bestpractice.com [ ]How does gemcitabine compare with non‐gemcitabine‐containing regimens for people with advanced pancreatic cancer?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2215/full显示答案 [ ]How do gemcitabine‐containing dual chemotherapy regimens compare with gemcitabine alone for people with advanced pancreatic cancer?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2216/full显示答案亚叶酸可增强氟尿嘧啶的效果，因此常与后者联合使用。 抑制胸苷酸合成酶，用于化疗的酶需要经胸腺嘧啶合成。

对于有局部病情进展（但无远处转移）、体力状态良好且正在或已完成化疗的患者，或者化疗有效的患者，可以通过放化疗或短期立体定向放疗 (SBRT) 进行巩固治疗，以进一步改善局部病情控制。[85]Balaban EP, Mangu PB, Khorana AA, et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016 Aug 1;34(22):2654-68.http://ascopubs.org/doi/full/10.1200/jco.2016.67.5561http://www.ncbi.nlm.nih.gov/pubmed/27247216?tool=bestpractice.com 探究放化疗或 SBRT 在局部晚期胰腺癌治疗中的作用的研究正在进行。

由于这种疾病的性质以及缺乏生存率统计数据，研究二线治疗选择的试验很有限，但已接受一线吉西他滨单药化疗且体力状态仍然很好的患者可能会获益于二线奥沙利铂、氟尿嘧啶和亚叶酸联合疗法。[86]Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9.http://ascopubs.org/doi/full/10.1200/jco.2013.53.6995http://www.ncbi.nlm.nih.gov/pubmed/24982456?tool=bestpractice.com

参考当地专科医生治疗方案作为剂量指导。

针对经选择患者组全部患者的治疗推荐

胰腺疼痛（腹痛和后背疼痛）处理起来较为麻烦

控制疼痛推荐从止痛阶梯入手，但吗啡也常用于止痛。

局部止痛应达成共识。 剂量应根据个体需求不同来调整，在症状缓解和副作用中寻求平衡。

此外适当使用长效阿片类镇痛药，经皮（或超声内镜引导下）腹腔内脏神经阻断或切除也可作为止痛的选择。[95]Kaufman M, Singh G, Das S, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol. 2010 Feb;44(2):127-34.http://www.ncbi.nlm.nih.gov/pubmed/19826273?tool=bestpractice.com[96]Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007519.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007519.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21412903?tool=bestpractice.com[97]Amr YM, Makharita MY. Comparative study between 2 protocols for management of severe pain in patients with unresectable pancreatic cancer: one-year follow-up. Clin J Pain. 2013 Sep;29(9):807-13.http://www.ncbi.nlm.nih.gov/pubmed/23917696?tool=bestpractice.com [ ]How does celiac plexus block affect compare with other analgesics in adults with pancreatic cancer pain?https://cochranelibrary.com/cca/doi/10.1002/cca.92/full显示答案

在日常饮食、营养补充中同时口服胰酶可保持体重和提高生活质量。[11]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955499/http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com

内镜下治疗优于手术方式。

然而切除失败的患者（尝试切除局部晚期肿瘤）可能从旁路手术获益，解决胆管和胃通道的梗阻，谓之双旁路途径，胆管旁路在胆汁经旁路引流中优于胆囊旁路，[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com 或者可能获益于预防性胃肠吻合术。[70]Huser N, Michalski CW, Schuster T, et al. Systematic review and meta-analysis of prophylactic gastroenterostomy for unresectable advanced pancreatic cancer. Br J Surg. 2009 Jul;96(7):711-9.http://www.ncbi.nlm.nih.gov/pubmed/19526616?tool=bestpractice.com

内镜支架置入术优于经肝塑料支架置入。[22]Pancreatic Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 (Suppl 5):v1-16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867803/http://www.ncbi.nlm.nih.gov/pubmed/15888770?tool=bestpractice.com

根据临床因素、部位的可行性还有专业经验来选择塑料型支架还是自膨胀金属支架。

塑料型支架寿命是3个月，如果患者一般状况较好、预后良好的话推荐使用金属支架。[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com证据 A不可切除性胰腺癌引起的梗阻性黄疸症状的缓解：高级别证据表明内镜下金属支架置入可解决胰腺癌引起的梗阻性黄疸。[69]Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004200.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625598?tool=bestpractice.com系统评价或者受试者＞200名的随机对照临床试验（RCT）。

针对经选择患者组全部患者的治疗推荐

每周吉西他滨单药治疗3/4周。一般状况差的患者姑息性治疗。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85[88]Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13.http://www.ncbi.nlm.nih.gov/pubmed/9196156?tool=bestpractice.com[89]Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018 Aug 20;36(24):2545-56.http://ascopubs.org/doi/full/10.1200/JCO.2018.78.9636http://www.ncbi.nlm.nih.gov/pubmed/29791286?tool=bestpractice.com证据 A生存率和临床获益于吉西他滨：高级别证据表明在姑息性治疗有症状的晚期胰腺癌方面，吉西他滨效果优于氟尿嘧啶， 研究同时表明接受吉西他滨治疗的患者比接受氟尿嘧啶治疗者的1年生存率高。[88]Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13.http://www.ncbi.nlm.nih.gov/pubmed/9196156?tool=bestpractice.com系统评价或者受试者＞200名的随机对照临床试验（RCT）。

吉西他滨的联合治疗联合铂类（奥沙利铂或顺铂）、氟嘧啶（氟尿嘧啶或卡倍他滨）、埃罗替尼（一种HER1/EGFR酪氨酸激酶抑制剂）或奥沙利铂、氟尿嘧啶和亚叶酸的联合疗法对于身体状况较好的患者更为有益。[36]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site[73]Sultana A, Tudur Smith C, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses. Br J Cancer. 2008 Jul 8;99(1):6-13.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453014/http://www.ncbi.nlm.nih.gov/pubmed/18577990?tool=bestpractice.com[74]Sultana A, Smith CT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2007 Jun 20;25(18):2607-15.http://ascopubs.org/doi/full/10.1200/JCO.2006.09.2551http://www.ncbi.nlm.nih.gov/pubmed/17577041?tool=bestpractice.com[75]Sultana A, Ghaneh P, Cunningham D, et al. Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison. BMC Cancer. 2008 Jul 8;8:192.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474853/http://www.ncbi.nlm.nih.gov/pubmed/18611273?tool=bestpractice.com[76]Poplin E, Feng Y, Berlin J, et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727286/http://www.ncbi.nlm.nih.gov/pubmed/19581537?tool=bestpractice.com[77]Heinemann V, Labianca R, Hinke A, et al. Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study. Ann Oncol. 2007 Oct;18(10):1652-9.https://academic.oup.com/annonc/article/18/10/1652/133336http://www.ncbi.nlm.nih.gov/pubmed/17660491?tool=bestpractice.com[79]Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8.http://ascopubs.org/doi/full/10.1200/JCO.2009.24.2446http://www.ncbi.nlm.nih.gov/pubmed/19858379?tool=bestpractice.com[80]Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6.http://ascopubs.org/doi/full/10.1200/JCO.2006.07.9525http://www.ncbi.nlm.nih.gov/pubmed/17452677?tool=bestpractice.com[81]Heinemann V, Vehling-Kaiser U, Waldschmidt D, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9.http://www.ncbi.nlm.nih.gov/pubmed/22773551?tool=bestpractice.com [ ]How do gemcitabine‐containing dual chemotherapy regimens compare with gemcitabine alone for people with advanced pancreatic cancer?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2216/full显示答案但临床试验中尚缺乏总生存率的获益证据。[90]Colucci G, Labianca R, Di Costanzo F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51.http://ascopubs.org/doi/full/10.1200/JCO.2009.25.4433http://www.ncbi.nlm.nih.gov/pubmed/20194854?tool=bestpractice.com[91]Dahan L, Bonnetain F, Ychou M, et al. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301). Gut. 2010 Nov;59(11):1527-34.http://gut.bmj.com/content/59/11/1527.longhttp://www.ncbi.nlm.nih.gov/pubmed/20947887?tool=bestpractice.com[92]Kulke MH, Tempero MA, Niedzwiecki D, et al. Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. J Clin Oncol. 2009 Nov 20;27(33):5506-12.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792952/http://www.ncbi.nlm.nih.gov/pubmed/19858396?tool=bestpractice.com 因一部分患者治疗反应良好（尚无生物指标去选择此类患者），这些联合化疗方案仍可适用于临床工作中。

在降低胰腺癌患者死亡率或不可切除胰腺癌患者的疾病进展时间方面，氟尿嘧啶和吉西他滨的联合化疗方案在应用1年时，并未较吉西他滨的单药化疗方案具有更多的优势。 然而，体力状态良好的转移性胰腺癌患者可使用 2 种新的治疗方案：FOLFIRINOX 治疗方案（亚叶酸、氟尿嘧啶、伊立替康、奥沙利铂）[84]Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.http://www.nejm.org/doi/full/10.1056/NEJMoa1011923#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/21561347?tool=bestpractice.com [ ]How does gemcitabine compare with non‐gemcitabine‐containing regimens for people with advanced pancreatic cancer?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2215/full显示答案或白蛋白结合型紫杉醇 (nab-paclitaxel) 与吉西他滨联用。[83]Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631139/http://www.ncbi.nlm.nih.gov/pubmed/24131140?tool=bestpractice.com 这两种治疗方案与吉西他滨单药治疗方案相比，均延长了生存期：FOLFIRINOX 组的中位总生存期为 11.1 个月，而吉西他滨组为 6.8 个月，[84]Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.http://www.nejm.org/doi/full/10.1056/NEJMoa1011923#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/21561347?tool=bestpractice.com 白蛋白结合型紫杉醇/吉西他滨组为 8.5 个月，而吉西他滨组为 6.7 个月。[83]Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631139/http://www.ncbi.nlm.nih.gov/pubmed/24131140?tool=bestpractice.com 尚未进行 FOLFIRINOX 与纳米微粒白蛋白结合型紫杉醇联合吉西他滨治疗的直接对比，因而两种治疗都可提供。[89]Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018 Aug 20;36(24):2545-56.http://ascopubs.org/doi/full/10.1200/JCO.2018.78.9636http://www.ncbi.nlm.nih.gov/pubmed/29791286?tool=bestpractice.com 

现在英国国家卫生与临床优化研究所 (NICE) 建议，对于那些活动自如或身体活动稍有受限的患者（东部肿瘤协作组体力状态为 0-1），将 FOLFIRINOX 作为一线治疗。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85

目前没有足够证据说明放化疗在治疗转移瘤方面优于单独化疗。[89]Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018 Aug 20;36(24):2545-56.http://ascopubs.org/doi/full/10.1200/JCO.2018.78.9636http://www.ncbi.nlm.nih.gov/pubmed/29791286?tool=bestpractice.com

已接受一线基于吉西他滨的单药化疗且体力状态仍然很好的患者可能会获益于二线奥沙利铂、氟尿嘧啶和亚叶酸联合疗法。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85[86]Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9.http://ascopubs.org/doi/full/10.1200/jco.2013.53.6995http://www.ncbi.nlm.nih.gov/pubmed/24982456?tool=bestpractice.com NICE 建议将基于吉西他滨的化疗作为二线治疗，用于接受一线 FOLFIRINOX 治疗后癌症继续进展的患者。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85 替代治疗方案是联合使用伊立替康脂质体和氟尿嘧啶，与氟尿嘧啶单药治疗相比，提高了总生存期（前者是 6.1 个月，后者是 4.2 个月）。[93]Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57.http://www.ncbi.nlm.nih.gov/pubmed/26615328?tool=bestpractice.com

参考当地专科医生治疗方案作为剂量指导。

针对经选择患者组全部患者的治疗推荐

胰腺疼痛（腹痛和后背疼痛）处理起来较为麻烦

控制疼痛推荐从止痛阶梯入手，但吗啡也常用于止痛。

局部止痛应达成共识。 剂量应根据个体需求不同来调整，在症状缓解和副作用中寻求平衡。

此外适当使用长效阿片类镇痛药，经皮（或超声内镜引导下）腹腔内脏神经阻断或切除也可作为止痛的选择。[49]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. February 2018 [internet publication].https://www.nice.org.uk/guidance/ng85[95]Kaufman M, Singh G, Das S, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol. 2010 Feb;44(2):127-34.http://www.ncbi.nlm.nih.gov/pubmed/19826273?tool=bestpractice.com[96]Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007519.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007519.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21412903?tool=bestpractice.com[97]Amr YM, Makharita MY. Comparative study between 2 protocols for management of severe pain in patients with unresectable pancreatic cancer: one-year follow-up. Clin J Pain. 2013 Sep;29(9):807-13.http://www.ncbi.nlm.nih.gov/pubmed/23917696?tool=bestpractice.com [ ]How does celiac plexus block affect compare with other analgesics in adults with pancreatic cancer pain?https://cochranelibrary.com/cca/doi/10.1002/cca.92/full显示答案

在日常饮食、营养补充中同时口服胰酶可保持体重和提高生活质量。[11]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955499/http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com