An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases

Broadhurst, Philip J. and Hart, Andrew R. (2020) An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases. Journal of Cancer Research and Clinical Oncology, 146 (5). pp. 1369-1375. ISSN 0171-5216

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Abstract

Purpose: Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. Methods: Patient notes with PDAC were reviewed at a large teaching hospital over 2 years. Study variables were obtained from multiple sources of information. Results: 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. Conclusion: Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin’s pharmacodynamic actions needs to be clarified.

Item Type: Article
Uncontrolled Keywords: drug absorption,metformin,pharmacokinetics,pancreatic cancer,trial eligibility
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 18 Mar 2020 07:18
Last Modified: 30 May 2020 23:56
URI: https://ueaeprints.uea.ac.uk/id/eprint/74527
DOI: 10.1007/s00432-020-03177-y

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