Toxicity patterns of cytotoxic drugs

Toxicity is a major concern for anticancer drugs. These compounds present a narrow therapeutic index, with a small difference between the dose required for an antitumor effect and that responsible for unacceptable toxicity. Their recommended doses are determined according to the toxicity endpoint. Moreover, toxicity is observed earlier than the therapeutic effect, so, toxic effects represent a major endpoint for pharmacodynamic studies of cytotoxic drugs. Knowledge of toxicity patterns and main factors of toxicity of anticancer drugs is required before modeling data of these studies. Hematological toxicities represent the main toxicity of the cytotoxic. However, non-hematological toxicities have become more important than hematological toxicities as pharmacodynamic endpoints in some circumstances such as high-dose chemotherapy associated with bone marrow transplantation. This paper will describe the main toxicity of the cytotoxic drugs, and its factors of both inter- and intra-patient variability. The toxicity pattern of topotecan will be examined as an example. Knowledge of the toxicity pattern of a drug consitutes a prerequirement before modeling its pharmacodynamics.