What impact might PK variability have on patient outcomes?
It has been well-established that 5-FU plasma levels correlate with the biological effects of the drug – both in terms of clinical efficacy and toxicity.207-209 Therefore, PK variations may have significant clinical consequences. For example, patients with low clearance rates of 5-FU may have higher plasma drug concentrations that can, in turn, result in serious toxicities. Conversely, patients with higher clearance rates may have drug levels that are not sufficient to achieve a therapeutic effect. These patients would be at risk of treatment failure and disease progression.207 When it comes to infusional 5-FU dosing, a recent study by Dr Erick Gamelin and his colleagues demonstrated that up to 85% of patients were not being optimally dosed.206,207-210These data underscore the importance of developing a more precise and rational method for dosing a drug that, in 2009, remains the foundation for colorectal cancer therapy.
