5-fluorouracil and its oral form, capecitabine or Xeloda®, are the cornerstones of treatment of a number of cancers, including colorectal, breast, oesophageal and head & neck. We all know that chemotherapy drugs can be extremely toxic; 15-20% of all patients receiving 5-FU will suffer severe side effects such as nausea, diarrhoea, stomatitis (oral inflammation), and decrease in white cells, among others. Up to 5% of patients will suffer extremely severe side effects and some will die as a consequence of their treatment.
Chemotherapy drugs, like all ingested or infused substances, are absorbed, distributed, metabolised and excreted from the body over time. For 5-FU, this process occurs very quickly – less than 5% of the drug remains in a patient’s bloodstream after one hour. Failure of this breakdown process means that systemic 5-FU levels quickly build up, leading to serious toxicity in 3% – 5% of patients. About 1% of the population is estimated to potentially suffer lethal consequences from even one dose of 5-FU because their bodies do not eliminate the drug properly.
An enzyme called DPD (dihydropyrimidine dehydrogenase) is believed to be responsible for the breakdown of 5-FU. So, in the past few years, researchers and some clinicians have administered genetic tests to determine whether 5-FU patients are deficient in DPD, leading to the risk of toxicity or death. But, apparently DPD does not tell us the whole story because some patients who show normal DPD levels go on to develop serious toxic side effects and others who have impaired DPD levels do not exhibit toxicity. In fact, the DPD test has been shown to correctly predict the risk of toxicity 50% of the time. As good as tossing a coin!
Saladax Biomedical Inc have developed a simple blood test for the measurement of 5-FU in plasma that can be easily performed by the routine hospital laboratory. Workers in Italy and the Netherlands have been developing a simple “5-FU clearance test”. The test is very simple: a very small dose of 5-FU (a fraction of the full dose that would not be enough to cause any harm) is administered to the patient and about one hour later a blood sample is taken and the 5-FU levels are measured. Since most of the 5-FU is typically excreted from the body within one hour, a patient with normal metabolic activity will have dramatically low blood levels of the drug. Patients who have a 5-FU clearance impairment will have elevated levels of 5-FU in their blood. With this information, the doctor can decide whether 5-FU is the drug of choice for his/her patient, and whether standard dosing should be modified to avoid undue toxicity.
We are excited to be involved in the development of this 5-FU clearance test as it represents a very simple, cost effective, practical approach to predicting 5-FU toxicity and helping to save lives and improve the quality of life for cancer patients during treatment.
Paul Kenny, European Key Account Manager