Impact of nutrition on pharmacokinetics of anti-neoplastic agents

It has been estimated that approximately 80% of the world's pediatric population lives in countries with limited resources, and that 43% of these children are malnourished. In children with cancer, malnutrition may antedate the diagnosis or be a result of aggressive chemotherapeutic regimens. Studies have shown that children with cancer and malnutrition have a less favorable prognosis, a higher risk of early relapse, and tolerate chemotherapy poorly when compared with children with normal nutritional status. Improvements in nutritional status may improve tolerance to chemotherapy. An understanding of the mechanisms responsible for the effects of malnutrition on drug disposition and pharmacodynamic response is important, especially for anti-neoplastic agents, which have a narrow therapeutic index and may be associated with potentially severe or life-threatening side-effects. Several factors related to malnutrition have been suggested to alter drug disposition. Diminished protein "status" in malnourished children results in lower amounts of plasma proteins, increasing the concentration of free drug available to exert its cytotoxic effect. Severely malnourished individuals also exhibit decreased oxidative metabolism and reduced glomerular filtration rate (GFR), potentially increasing concentrations of parent drug or active metabolites. Malnourished children receiving chemotherapy for the treatment of an underlying malignancy may need specifically "tailored" protocols to achieve therapeutic response while minimizing adverse acute and long-term side effects. The role of specific interventions, such as correction of nutritional status or pharmacokinetic drug monitoring, should be evaluated in this context.