Modeling antitumor activity in xenograft tumor treatment.

To analyze responses of solid tumors to treatment with antitumor therapy, we applied nonparametric mixed-effects models to investigate tumor volumes measured over a fixed. The population and individual response functions were approximated by penalized splines. Linear mixed-effects modeling was applied in the implementation of the estimation. We applied the approach to an analysis of a real xenograft study of a new antitumor agent, temozolomide, combined with irinotecan. The model fitted the data very well. We conducted a sensitivity analysis to determine the effect of informative dropout. We also propose an intuitive approach to a comparison of the antitumor effects of two different treatments. Biological interpretations and clinical implications are discussed.