Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.
Liver Int. 2019 May;39 Suppl 1:123-142. doi: 10.1111/liv.14100.
Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention-to-treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first-line treatment of patients with advanced disease; there is no established second-line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on-target therapeutic options are under active investigation. The most developed are studies targeting IDH-1 (isocitrate dehydrogenase) mutations and FGFR-2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed.
大多数胆管癌（CCA）患者就诊时已处于晚期（不可切除或转移性），接受潜在治愈性切除的患者复发率较高。随着随机临床试验（RCT）的出现以及对CCA 潜在分子机制的深入了解，先前对晚期疾病患者的治疗消极态度已被积极的临床研究所取代。最近有三项 RCT 评估了根治性切除术后辅助化疗；其中只有一项有可能改变实践。BILCAP 研究未能通过意向治疗分析达到其主要终点；然而，一项预先计划的敏感性分析（主要调整淋巴结状态）显示出生存获益。这一点，再加上中位总生存期的数值差异，导致许多临床医生采用了辅助卡培他滨。对于晚期疾病患者，唯一可用的一级数据支持顺铂和吉西他滨用于晚期疾病患者的一线治疗；目前尚无既定的二线化疗方案。先前针对靶向治疗的尝试均未成功（即针对表皮生长因子受体和血管内皮生长因子途径）。越来越多的基因组亚型正在被定义；对于其中一些，针对特定靶点的治疗方案正在积极研究中。最成熟的研究是针对 IDH-1（异柠檬酸脱氢酶）突变和 FGFR-2（成纤维细胞生长因子受体）融合的研究，早期结果令人鼓舞。其他几条途径正在评估中，同时也在进行早期针对免疫环境的研究；这些研究还处于早期阶段，迄今为止还没有改变实践。讨论了这些新出现的治疗方法。
