Re: Antitumor Efficacy Testing in Rodents

Extract

In her thorough commentary, Hollingshead ( 1 ) discussed the key to successfully conducting in vivo antitumor efficacy testing in rodent models. She identified as crucial the appropriate choice of different items, such as tumor models, experimental conditions, dosing regimens, experimental endpoints, and statistics for comparing experimental groups. We agree that the adoption of standardized experimental conditions increases the relevance of the preclinical experiments in rodents ( 2 ).

However, the efficacy endpoints mentioned in the commentary usually adopted in these studies (percentage test to control tumor weight ratio, median time to a defined tumor weight, etc.), are dose-, schedule-, and time-dependent metrics. We demonstrated that changing the dose level and/or the duration of the treatment of an anticancer agent achieved the maximal value of tumor growth inhibition at different time points, which could not be easily anticipated based on the experimental conditions ( 3 ). The dose dependence, schedule dependence, and time-dependence of these metrics may explain the number of different experiments needed to characterize a new compound and compare it with other drugs. This dependence on experimental conditions not only affects time and cost of drug development but also fosters criticism on the usefulness of these rodent models.