The chemotherapy drug, 5-fluorouracil (5-FU), or its oral pro-drug capecitabine, are commonly used in treating oesophageal and gastric cancer. The dose a patient receives is currently determined using body surface area. This approach, however, produces outcomes ranging from poor efficacy to toxicity including mouth ulcers, diarrhoea or life threatening febrile neutropenia.

Studies have shown that taking a venepuncture blood sample after the first dose of 5-FU and using this to personalise dosing for subsequent treatments, improves efficacy of treatment and reduces toxicity. Venepuncture blood sampling requires a needle to be placed in patient’s arm vein and blood withdrawn by syringe. It requires blood collection by trained health professionals and may produce patient discomfort – often minor but not always. Frequent post-chemotherapy blood sampling is also time-consuming and uncomfortable for patients. Recently, devices have become available that enable small blood samples to be taken using a simple fingerprick (like diabetic patients do to monitor blood sugar). This type of sampling could be easily performed by staff in the chemotherapy suite, or more remotely in GPs offices or by patients at home. This study will investigate whether blood sampling by fingerprick instead of venepuncture is simpler, reliable and sufficiently sensitive to provide the blood concentration data for personalising each patient’s dose. It will also gather information on the acceptability of fingerprick blood sampling to the patient. Validation of this approach with 5-FU could lead to similar studies of other drugs used in esophageal cancer, including carboplatin and paclitaxel, as well as in other cancers.

An additional complication with 5-FU therapy is that ~1% of patients will experience life-threatening toxicity after their first dose as they lack an enzyme which breaks down 5-FU. While different methods to identify these patients have been reported in the scientific literature, few provide a reliable or easy to do clinical method of identification. Since patients undergoing chemotherapy often have a blood sample taken prior to treatment, for this study consenting patients would have an extra 3mL of blood taken to enable us to investigate a new method to assess enzyme activity. This would involve adding the drug to the patent’s sample in the laboratory and measuring the rate of breakdown of the drug. Patients with little enzyme activity should show slow breakdown of the drug. In this pilot study we will not use these results for dose adjustment and the normal dosing method would be used. However, if this test does show promise, this would provide pilot data for a much larger study where the approach could be validated.

This study would provide essential information on the plausibility of using these two approaches (fingerprick and pre-drug testing) for personalised dosing of 5-FU in patients with oesophageal cancer. Fingerprick blood testing would enable patients located in regional and rural centres alike to have access to better dosage adjustment to optimise treatment and a pre-treatment enzyme activity blood test could dramatically reduce the incidence of severe toxicity with this drug.

Researchers 

A/Prof Jennifer Schneider, Prof Stephen Ackland, Prof Jennifer Martin, Dr Peter Galettis, Dr Catherine Lucas, Ms Madhu Garg

Research Area 
Project type 
Project Grant
Year of funding 
2017