Bien Harold, Mackenzie Gerardo G, Choi Minsig
Stony Brook University, Department of Medicine, Division of Hematology/Oncology, HSC 15-053C, 101 Nicholls Rd, Stony Brook, NY 11794-8191, USA.
Recent Pat Anticancer Drug Discov. 2016;11(4):376-383. doi: 10.2174/1574892811666160729094415.
Effective therapies against metastatic pancreatic cancer remain limited, and despite treatment, many will ultimately progress. Previously, few options were available for second line therapy in metastatic pancreatic cancer. Liposomal encapsulated irinotecan, in combination with leucovorin-modulated fluorouracil, was found to significantly increase overall survival in patients who have progressed after gemcitabine- based therapy in a large, international, randomized clinical trial (NAPOLI-1). We reviewed the background of systemic therapy for metastatic pancreatic cancer, examined putative mechanisms for the success of encapsulated drugs, and identified recent patent applications on the use of liposomal irinotecan in pancreatic cancer. The landmark NAPOLI-1 trial established a second-line option for those with metastatic pancreatic cancer refractory to gemcitabine chemotherapy, but effective therapies with long duration of response are still lacking. Alternative techniques targeting key driver genes in pancreatic cancer and novel methods of early detection and targeting drugs are currently being explored. How liposomal irinotecan can be integrated into chemotherapy regimens, including neoadjuvant or first line combinations, are currently being tested in clinical trials and covered by several new patent applications.
针对转移性胰腺癌的有效治疗方法仍然有限,尽管进行了治疗,许多患者最终仍会病情进展。以前,转移性胰腺癌二线治疗的选择很少。在一项大型国际随机临床试验(NAPOLI-1)中,发现脂质体包裹的伊立替康联合亚叶酸调节的氟尿嘧啶可显著提高在基于吉西他滨的治疗后病情进展的患者的总生存期。我们回顾了转移性胰腺癌全身治疗的背景,研究了包裹药物成功的假定机制,并确定了关于脂质体伊立替康在胰腺癌中应用的近期专利申请。具有里程碑意义的NAPOLI-1试验为那些对吉西他滨化疗难治的转移性胰腺癌患者确立了二线治疗选择,但仍缺乏具有长期缓解效果的有效治疗方法。目前正在探索针对胰腺癌关键驱动基因的替代技术以及早期检测和靶向药物的新方法。脂质体伊立替康如何融入化疗方案,包括新辅助或一线联合方案,目前正在临床试验中进行测试,并且有几项新的专利申请涵盖了这方面内容。