Abstract
Nonclinical toxicity studies of anticancer agents are conducted to understand their profiles such as target organs, exposure-response relationships, and reversibility, same as other pharmaceuticals. However, unlike drugs for non-oncology indication, anticancer drugs have been known often to have narrow or negative safety margin expressed as exposure multiple between systemic exposure at nonclinical efficacious dose/predicted efficacious dose in humans and that at toxic dose in the toxicity study. This means that it is important to evaluate the reversibility of the anticancer agents’ toxicity from the perspective of clinical development and risk assessment.
For the correct judgement of the reversibility in histopathological examination, it is essentially critical to understand lesions including their severity and pathological stage accurately and to express them using appropriate terminology and grades at the end of the dosing period. Then, the characteristics of the findings at the end of the recovery period are to be carefully evaluated to examine whether they recovered rapidly after the end of the administration period, were in the middle of recovery, or did not recover at all. When the lesions are determined to be in the process of recovery, the length of time required for complete recovery is sometimes estimated considering the turnover of affected cells. This process requires the knowledge of histology and physiology as well as the knowledge of pathology.
In this symposium, we will introduce the lesions and reversibility observed in organs such as the gastrointestinal tract, lymphohematopoietic system, and testes, which are often injured by anticancer agents, focusing on histopathological images.
