[Cytotoxic chemotherapy in elderly patients: present and future]

Cancer in elderly people accounts for more than 50% of the malignant tumors treated per year in France and this population of patients has a rather high-life expectancy. Chemotherapy is active in these elderly patients but clearly more toxic than for young ones. The general tendency among the physicians to empirically reduce the doses is due to the known increased risk of unexpected toxicities. That is why there is such a large variety of conflicting opinions in the literature concerning the benefit and toxic effects of cytostatic drugs in the elderly. Therefore, it appears consistent to adjust chemotherapy regimen according to physiological criteria. Among them is biological age which is a better parameter than chronological age to describe the biological heterogeneity of this population of patients. Nakamura et al have published an interesting model for the calculation of biological age by principal component analysis using 11 easily measurable biological and clinical variables in a series of healthy elderly people. This kind of approach is not at present available for cancer patients but it allows to demonstrate that the chronological age is only one among many other age-related variables and is not sufficient to fully describe it. The variations in pharmacokinetic data are more frequent in the elderly than in younger people and this reflects age-related physiological heterogeneity. This factor is well taken into account in recently described population pharmacokinetic models, bayesian fittings and adaptative control which may represent promising approaches of cytostatics dose adjustments. Such models have been successfully developed in young patients receiving doxorubicin, methotrexate, melphalan and teniposide. They require a low number of blood samples to determine individual parameters and further adjust the doses, and are therefore of potential interest in old patients. Prospective studies are warranted in the future in order to recommend their use in the elderly.