imulations showing long-term tumor xenograft response to combination therapy.

<p>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>, the administration of a weekly dose of 30 mg/kg carboplatin together with a daily dose of 100 mg/kg ABT-737 is simulated, and simulations allowed to run until tumor cell numbers averaged over 7 days (the period of carboplatin administration) achieve a steady-state. <b>A</b>, Predicted steady states of average tumor cell numbers as a function of carboplatin infusion time . As is increased from 0 hours (corresponding to a bolus dose) to 120 hours, the average tumor cell number steady-state decreases rapidly to (see inset), and then increases, with minimal survival of tumor cells predicted for . <b>B</b>, Predicted values of , the length of time therapy must be administered to achieve minimal residual disease (defined as cell remaining) as is varied between 1 and 25 hours. A minimum value of days is predicted for weekly carboplatin infusions lasting 8 hours. <b>C</b>, Minimum values of are predicted to decrease to 215 days as , the arrested cell sensitivity to intracellular Bax is increased. In all cases, a carboplatin infusion time of 8 hours minimized the cure time.