A collaborative research team from the University of Auckland and Auckland City Hospital has launched a groundbreaking clinical trial to investigate the cardiac safety profile of 5-fluorouracil (5FU), a cornerstone chemotherapy drug used in cancer treatment for over five decades.
The study, led by Dr. Nicky Lawrence and Professor Nuala Helsby from Waipapa Taumata Rau, University of Auckland, alongside Auckland Hospital oncologist Dr. Jane So, aims to unravel the mechanisms behind potentially fatal cardiotoxicity observed in approximately 5% of patients receiving 5FU treatment.
Understanding 5FU Cardiotoxicity
"It's a really old drug, but there are still all these undiscovered things about it. No one has put all the information together to say 'ah, this is why we might be seeing the side effects,'" explains Professor Helsby, from the Department of Molecular Medicine and Pathology.
Despite its cardiac risks, 5FU remains the primary chemotherapy option for stomach and bowel cancers due to its superior efficacy. Dr. Lawrence, who serves as the director of Cancer Trials New Zealand and senior lecturer in medical oncology, emphasizes the drug's critical role in current treatment protocols.
Innovative Research Methodology
The pilot trial seeks to recruit 10 patients who will undergo comprehensive monitoring during their first chemotherapy cycle. Participants will wear Holter monitors for 48 hours while receiving 5FU infusion, complete three blood tests, and provide urine samples. This multi-modal approach will help researchers track cardiac activity and drug metabolism patterns.
Professor Helsby hypothesizes that adverse reactions might be linked to individual variations in drug metabolism: "We think there might be products people's bodies make as they break down 5FU that could be causing these side effects, so we want to know who is making too much of these products."
Advanced Monitoring Technologies
The research team will implement new software designed to detect subtle ECG changes through Holter monitoring, potentially identifying early warning signs of cardiac complications. Currently, there are no reliable methods to predict which patients will experience severe cardiac side effects, leading to treatment discontinuation when chest pains occur.
Funding and Future Implications
The research has secured substantial funding, including $149,421 from the Gut Cancer Foundation and $28,968 from the University's Te Aka Mātauranga Matepukupuku – Centre for Cancer Research. Additional support comes from the Cancer Society and Canopy Cancer Care.
If the pilot study successfully recruits its target number of patients, the researchers plan to expand their investigation into a larger national study. The findings could revolutionize 5FU administration by enabling physicians to identify at-risk patients and potentially develop strategies to maintain treatment in those who might otherwise have to discontinue this effective therapy.
