Thota Ramya, Maitra Anirban, Berlin Jordan D
From the *Division of Hematology/Oncology, Vanderbilt University, Nashville, TN; and †Sheikh Ahmed Pancreatic Cancer Research Center, Departments of Pathology and Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX.
Pancreas. 2017 Feb;46(2):143-150. doi: 10.1097/MPA.0000000000000753.
Prior phase III trials in advanced pancreatic cancer have been predominantly unsuccessful. In this review, we attempt to understand how past preclinical data were translated into phase III clinical trials in metastatic pancreatic cancer as described in the article. A systematic literature review conducted through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, from January 1997 to June 2015 using key words-phase III clinical trials, metastatic/advanced pancreatic adenocarcinoma or pancreatic cancer identified 30 randomized controlled trials (RCTs) that met criteria. The trials were limited to RCTs in the first-line treatment of patients with metastatic pancreatic cancer. The success rate of first-line phase III studies in advanced pancreatic cancer was only 13%. In 60% of the RCTs, no preclinical experiments were referenced in biologically cognate pancreatic models. Nine (30%) of the RCTs were designed based on preclinical evidence from in vitro cell lines alone without additional in vivo validation in xenograft models. It remains uncertain how strongly the preclinical data influence the development of clinical regimens but so far the studies developed based on more solid preclinical evidence have been successful.
先前针对晚期胰腺癌的III期试验大多未取得成功。在本综述中，我们试图了解如文章所述，过去的临床前数据是如何转化为转移性胰腺癌的III期临床试验的。通过MEDLINE、Embase和Cochrane对照试验中央注册库数据库，使用关键词“III期临床试验”、“转移性/晚期胰腺腺癌或胰腺癌”，对1997年1月至2015年6月期间的文献进行系统回顾，共识别出30项符合标准的随机对照试验（RCT）。这些试验仅限于转移性胰腺癌患者一线治疗的RCT。晚期胰腺癌一线III期研究的成功率仅为13%。在60%的RCT中，在生物学相关的胰腺模型中未引用临床前实验。其中9项（30%）RCT仅基于体外细胞系的临床前证据设计，未在异种移植模型中进行额外的体内验证。临床前数据对临床方案的制定有多大影响仍不确定，但迄今为止，基于更可靠的临床前证据开展的研究已取得成功。
