  In concurrent chemoradiotherapy, chemotherapeutic agents are administered
during the course of radiotherapy to enhance the primary tumor control.
However, that often comes at the expense of increased risk of normal-tissue
complications. The additional biological damage is mainly attributed to two
mechanisms of action, which are the independent cytotoxic activity of
chemotherapeutic agents and their interactive cooperation with radiation. The
goal of this study is to develop a mathematical framework to obtain drug and
radiation administration schedules that maximize the therapeutic gain for
concurrent chemoradiotherapy. In particular, we analyze the impact of
incorporating these two mechanisms into the radiation fractionation problem.
Considering each mechanism individually, we first derive closed-form
expressions for the optimal radiation fractionation regimen and the
corresponding drug administration schedule. We next study the case in which
both mechanisms are simultaneously present and develop a dynamic programming
framework to determine optimal treatment regimens. Results show that those
chemotherapeutic agents that interact with radiation may change optimal
radiation fractionation regimens. Moreover, administration of chemotherapeutic
agents possessing both mechanisms may give rise to optimal non-stationary
radiation fractionation schemes.
