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Abstract
An important limitation in the use of chemotherapy in cancer treatment is that cytotoxic
agents have small margins of safety compared with other drugs. The largely unpredictable
pharmacokinetics of cytotoxic agents contribute significantly to differences in toxicity
and efficacy between individuals. Over the past few decades, evidence has accumulated
that the inflammatory response to conditions such as infection, degenerative disease,
and cancer can greatly affect the disposition of drugs. A more recent finding is that
the presence of an inflammatory response identifies patients with more aggressive
disease and may also compromise the pharmacodynamics of anticancer drugs. In this
review, we discuss the changes in the pharmacokinetics of drugs caused by the presence
of inflammation. Also, we discuss the modulating role of inflammatory mediators on
the pharmacokinetics and pharmacodynamics of cytotoxic agents. We argue that, overall,
these factors identify inflammatory response as a potentially important factor in
the interindividual variability of response and toxic effects to cancer chemotherapy.