Springfeld Christoph, Jäger Dirk, Büchler Markus W, Strobel Oliver, Hackert Thilo, Palmer Daniel H, Neoptolemos John P
Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany.
Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany.
Presse Med. 2019 Mar;48(3 Pt 2):e159-e174. doi: 10.1016/j.lpm.2019.02.025. Epub 2019 Mar 15.
Chemotherapy is an important part of multimodality pancreatic cancer treatment. After curative resection, adjuvant chemotherapy can significantly improve disease free survival and overall survival. The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years. Patients not fit for combination chemotherapy however may still benefit from gemcitabine. Patients with good performance status may benefit from second-line chemotherapy. Chemoradiation has long been used in locally advanced pancreatic cancer but is now tempered following the LAP07 study. This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation and local anti-KRAS therapy (using siG12D-LODER) are currently under investigation. Given the systemic nature of pancreas cancer from an early stage, the success of any local approach other than complete surgical resection (with adjuvant systemic therapy) is likely to be very limited. In patients with locally advanced, irresectable cancer, chemotherapy may offer the chance for secondary resection with a survival similar to patients with primary resectable disease. Downstaging regimens need to be evaluated in prospective randomized trials in order to make firm recommendations. Selection of patient groups for specific therapy including cytotoxics is becoming a reality using assays based on drug cellular transport and metabolism, and molecular signatures. Going forward, high throughput screening of different chemotherapy agents using molecular signatures based on patients' derived organoids holds considerable promise.
化疗是胰腺癌多模式治疗的重要组成部分。根治性切除术后，辅助化疗可显著提高无病生存期和总生存期。目前的标准治疗方案是，对于适合该方案的患者，采用亚叶酸钙、5-氟尿嘧啶、伊立替康和奥沙利铂（mFOLFIRINOX）进行6个月的辅助化疗；否则，根据欧洲胰腺癌研究组（ESPAC）-4研究，采用吉西他滨和卡培他滨进行6个月的治疗。对于转移性疾病患者，根据FOLFIRINOX方案或吉西他滨联合纳米白蛋白结合型紫杉醇进行联合化疗，是对多年来一直作为标准治疗的吉西他滨单药治疗的重要改进。然而，不适合联合化疗的患者仍可能从吉西他滨治疗中获益。体能状态良好的患者可能从二线化疗中获益。放化疗长期以来一直用于局部晚期胰腺癌，但在LAP07研究之后，其应用有所调整。该试验表明，在接受吉西他滨（联合或不联合厄洛替尼）治疗4个月后疾病稳定的患者中，随机分为继续吉西他滨治疗组或放化疗组（54Gy联合卡培他滨），两组的总生存期无差异。作为放疗的替代方法，目前正在研究其他形式的局部治疗，包括射频消融、不可逆电穿孔、高强度聚焦超声、微波消融和局部抗KRAS治疗（使用siG12D-LODER）。鉴于胰腺癌从早期就具有全身性，除了完整的手术切除（联合辅助全身治疗）外，任何局部治疗方法的成功可能性都可能非常有限。对于局部晚期、不可切除的癌症患者，化疗可能提供二次切除的机会，其生存期与原发性可切除疾病患者相似。需要在前瞻性随机试验中评估降期方案，以便提出明确的建议。利用基于药物细胞转运和代谢以及分子特征的检测方法，为特定治疗（包括细胞毒性药物治疗）选择患者群体正在成为现实。展望未来，基于患者来源的类器官的分子特征对不同化疗药物进行高通量筛选具有很大的前景。
