title: Preclinical Rationale for the Phase III Trials in Metastatic Pancreatic Cancer: Is Wishful Thinking Clouding Successful Drug Development for Pancreatic Cancer?
abstract: 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.
authors.affiliation: 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.
authors.forename: Ramya
authors.initials: R
authors.lastname: Thota
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Berlin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004358:Drug Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic / Q000379:methods