Optimizing carboplatin and ABT-737 doses when given in combination.

<p><b>A</b>, Predicted Combination Index (CI) values computed for a desired tumor growth inhibition level of 67%, for various combinations of carboplatin and ABT-737. Following the experimental protocol in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081582#pone.0081582-Witham1" target="_blank">[13]</a>, treatment is initiated at 19 days post-transplantation and continued for 4 weeks. Simulations indicate that a combination of 17.8 mg/kg carboplatin given weekly combined with a daily dose of 86.5 mg/kg ABT-737 minimizes the CI and hence maximizes the synergy between the two drugs (dashed lines). <b>B</b>, Predicted tumor growth dynamics corresponding to the optimal dose combination found above. Plots show tumor cell numbers averaged over 7 days (the period of carboplatin administration) versus time. <b>C</b>, Predicted time-courses of tumor growth inhibition levels as compared to the control (no treatment) case, corresponding to the optimal dose combination found above.