Factors involved in clinical pharmacology variability in oncology (review)

One of the major problems in cancer pharmacology is the prediction of the outcome of treatment in terms of both toxicity and tumor response. Indeed, why is a patient presenting a high toxicity at a standard dose? Also, why is another patient presenting a response to chemotherapy, while another does not respond, even if the same doses and drugs are used? The causes of variability in the response to chemotherapy can be classified in 2 classes, these related to the host, and those related to the tumor. Concerning the host, physiopathological parameters can influence the outcome of treatment e.g. age, sex, kidney and liver functions, plasma protein binding, concomitant treatments, and pharmacogenetics. With regard to the tumor, many factors can also influence chemotherapy e.g. tumor type, localization, volume, aggressiveness, dissemination stage, prior treatments (resistance), biological marker levels, and pharmacogenetic phenotype. Although some progress has been made in the past years concerning the clinical use of some factors responsible for the variability of pharmacological response in oncology, much remains to be done in order to adapt the treatment to a particular patient. Although pharmacogenetic phenotyping has been feasible for some anticancer drugs, this area deserves more effort in the future. Indeed, pharmacogenetic phenotyping of both the patient and the tumor will probably allow to tailor chemotherapy to an individual patient, in order to optimize the patient's chances to obtain a tumor response with minimum systemic toxicity.