腫瘍学における薬剤：動物毒性試験で認められる標的臓器所見

Nonclinical testing is mandatory for oncology drugs prior to starting clinical studies and includes animal toxicity evaluation. As these drugs can be toxic by their nature, such testing is used to identify potential target organs that may equate to toxicity in the clinic and allow for careful patient monitoring. An evaluation of toxicity studies in rodents and non-rodents, used to support clinical entry, for 60 small molecule oncology drug candidates (including tyrosine kinase inhibitors) was performed to identify target organ across a full range of body systems. It was shown the most affected ones were lymphoid, gastrointestinal, bone marrow/hematologic and liver for both rodent and non-rodent. The next most affected body systems were kidney and male reproductive organs (rodent and non-rodents) along with female reproductive organs, endocrine, bone and skin (rodents, and with a lower frequency in non-rodents). None of these findings prevented clinical entry. It was also shown that drug candidate target organs were largely independent of tumor site interaction (whether cell nucleus, cytoplasm proteins or membrane receptors). Overall, this evaluation confirmed the importance of toxicity testing before exposing patients to oncology drug candidates but opens discussion on whether the extent of our current testing paradigm could be reduced.