Source:Current Problems in Cancer
Author(s): Jennifer Harrington, Louise Carter, Bristi Basu, Natalie Cook
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 [1,2] , 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 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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