Oncolytic adenoviruses and the treatment of pancreatic cancer: a review of clinical trials

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) remains a common and difficult cancer to treat. Surgical resection and chemotherapy are standard of care and clinical outcomes remain poor. Oncolytic adenoviruses are a unique approach to the treatment of this challenging cancer, aiming to overcome the features of this disease that pose the key obstacles to standard therapies. This paper provides a detailed review of the clinical trials of conditionally-replicative adenoviruses in pancreatic cancer to date, with a brief summary of the past preclinical literature and future prospects of this therapy. METHODS: MEDLINE, Embase, and clinicaltrials.gov were searched from inception to December 23rd 2022 for clinical trials of conditionally-replicative adenoviruses used in patients with pancreatic ductal adenocarcinoma. Primary features for review included patient demographics, treatment protocol including dose and administration route, adverse events, patient responses and survival rates. RESULTS: The six published clinical trials suggest that objective clinical responses can be achieved with a tolerable level of side effects, even at high viral doses. The more clinically adaptable intravenous route of administration also appears to be as well tolerated as the more challenging intratumoural injections. CONCLUSION: Published clinical trials provide data of the safety and some signs of oncolytic activity of conditionally-replicative adenoviruses in patients with pancreatic cancer. Importantly, on the latest trials, the easier intravenous route of administration seems to be well tolerated and safe, providing the opportunity for further clinical evaluation. It is hoped that the ongoing clinical trials will yield more promising results of this therapeutic approach against a currently intractable disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-023-04735-w.