Benefits of personalized dosing of 5-fluorouracil: decreased side effects and improved outcomes

This study evaluated the benefits of personalized 5-fluorouracil (Efudex) dosing in early and late-stage colorectal cancer patients.

5-fluorouracil has been a mainstay of colorectal cancer chemotherapy for over 50 years. Research has shown that in order for 5-fluorouracil to work effectively target concentrations need to be achieved in the blood. Currently only 20% to 30% of patients achieve the required therapeutic dose using standard dosing techniques. Standard dosing is calculated based on the patients’ body surface area (BSA).

Another dosing technique involves monitoring patients’ blood levels of 5-fluorouracil and then personalizing their dose of drug. The benefits of personalized dosing for patients with advanced cancer (cancer that has spread to distant sites) is known. However, personalized dosing for the treatment of early-stage colorectal cancer has not been reported. It may improve patient outcome and decrease side effects.

The medical reports of 84 patients with colorectal cancer were included in this study. 49 patients had cancer that had spread to distant sites (stage IV) and 35 patients had cancer that had reached the outer layer of the intestine or spread to the lymph nodes (stage II/III). All patients were treated with either mFOLFOX6 (modifiedFOLFOX6; modified 5-fluorouracil, leucovorin, oxaliplatin (Eloxatin]) or mFOLFIRI (modified 5-fluorouracil, leucovorin, irinotecan [Camptosar]).

The dose of 5-fluorouracil was calculated based on the standard technique for 46 patients. The remaining 38 patients received their doses of 5-fluorouracil based on their own blood levels (personalized dosing).

Personalized dosing significantly improved disease-free survival (length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer) in stage II/III patients. There was also a trend towards improved progression-free survival (time following treatment before the disease progresses) among stage IV patients who had personalized dosing.

Personalized dosing reduced the occurrence of adverse events in stage II/III patients (32% compared to 69% in the standard technique group). Gastrointestinal side effects (diarrhea, nausea, vomiting and dehydration) were the most common adverse events experienced by patients.  

Personalized dosing also delayed the onset of adverse events in stage II/III patients. Adverse events occurred after the second 5-fluorouracil dose in the standard technique group and after the sixth to seventh dose after personalized dosing.

The authors concluded that personalized dosing of 5-fluorouracil is potentially beneficial for early and late stage colorectal cancer patients. Personalized dosing helped reduce number of adverse events and delayed the onset of adverse events.

This is an early study with a relatively small number of patients. Future studies are needed to ensure the accuracy of the results.