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Drug Development and Clinical Trial Design in Pancreatico-biliary malignancies

Accepted version
Peer-reviewed

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Type

Article

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Authors

Harrington, Jennifer 
Carter, Louise 
Cook, Natalie 

Abstract

Abstract Pancreatico-biliary tumours arise from the pancreas, bile duct and Ampulla of Vater. Despite their close anatomical location, they have different aetiology and biology. However, they uniformly share a poor prognosis, with no major improvements observed in overall survival over decades, even in the face of progress in diagnostic imaging, surgical techniques and advances in systemic and loco-regional radiation therapies. To date, cytotoxic treatment has been associated with modest benefits in the advanced disease setting, and survival for patients with stage IV disease has not exceeded a year. Therefore, there is a pressing need to identify better treatments which may impact more significantly. Frequently, encouraging signals of potential efficacy for novel agents in early phase clinical trials have been followed by disappointing failures in larger Phase III trials , raising the valid question of how drug development can be optimised for patients with pancreatic adenocarcinoma and biliary tract malignancies (P-B tumours). In this paper we summarise the current therapeutic options for these patients and their limitations. The biological context of these cancers is reviewed, highlighting features that may make them resistant to standard chemotherapeutics and could be potential therapeutic targets. We will discuss the role of early phase clinical trials, defined as Phase I and non-randomised Phase 2 trials, within the clinical context and current therapeutic landscape of P-B tumours and postulate how translational studies and trial design may enable better realisation of emerging targets together with a proposed model for future patient management. A detailed summary of current Phase I clinical trials in P-B tumours is provided.

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Keywords

Biliary tract cancer, Clinical trial design, Experimental therapeutics, Pancreatic cancer, Animals, Antineoplastic Agents, Biliary Tract Neoplasms, Clinical Trials as Topic, Drug Development, Drug Screening Assays, Antitumor, Drugs, Investigational, Humans, Pancreatic Neoplasms, Research Design, Tumor Microenvironment

Journal Title

Current Problems in Cancer

Conference Name

Journal ISSN

0147-0272
1535-6345

Volume Title

42

Publisher

Elsevier
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