Capecitabine: Have we got the dose right?

In the past 5-10 years there has been a growing trend for substituting conventional 5-fluorouracil with the oral prodrug of 5-fluorouracil, capecitabine, in chemotherapy regimens. This regimen change is based on evidence of the efficacy equivalence of these two drugs and the lack of an increase in overall toxic effects when capecitabine is used. Many investigators in different parts of the world have determined their own starting dose for capecitabine, usually based on their experience of toxic events within the population of patients they treat. This starting dose is usually between 1,000-1,250 mg/m2, which is generally administered twice daily for 14 days followed by 7 days rest. This Review summarizes why there may indeed not be a universally applicable starting dose for capecitabine because of interpatient differences in basic physiology, pharmacogenomics and diet. This article also explores which of these factors contribute to the observed inter-regional geographical variation in capecitabine toxicity, and explains why even within a region various factors should prompt a clinician to modify the starting dose.