Assessing cytotoxic treatment effects in preclinical tumor xenograft models

In preclinical solid tumor xenograft experiments, tumor response to cytotoxic agents is often assessed by tumor cell kill. Log10 cell kill (LCK) is commonly used to quantify the tumor cell kill in such experiments. For comparisons of antitumor activity between tumor lines, the LCK values are converted to an arbitrary rating; for example, the treatment effect is considered significant if the LCK>0.7 (Corbett et al., 2003). The drawback of using such a predefined cutoff point is that it does not account for the true variation of the experiments. In this article, a nonparametric bootstrap percentile interval of the LCK is proposed. The cytotoxic treatment effect can be assessed by the confidence limits of the LCK. Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method.