Assessing Cytotoxic Treatment Effects in Preclinical Tumor Xenograft Models

Abstract

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.

Key Words:

• Bootstrap
• Confidence interval
• Log10 cell kill
• Right censoring
• Xenograft

ACKNOWLEDGMENTS

The authors are thankful to the editor and anonymous referees whose careful reading and constructive comments improved the earlier version of this article. The work was supported in part by National Cancer Institute (NCI) support grants CA21765 and N01-CM-42216 and the American Lebanese Syrian Associated Charities (ALSAC).

Notes

·Indicates a missing value due to mouse sacrificed after its tumor quadrupled.

•Indicates that mouse died due to toxicity.

*Indicates a censoring.

t _D and t _Q are the tumor doubling and quadrupling times, respectively.