Abstract
This chapter contains a review of the potential of radioand chemotherapy to eradicate tumor cells. With regard to the amount of quantitative cell kill, important differences exist between ionizing radiation and chemotherapy. In principle, radiation treatment can be designed to cover the whole tumor with a homogeneously distributed full radiation dose, capable of inactivation of all tumor cells. In contrast, pharmacotherapy is limited by the fact that the dose of the active, cell-killing form of the compound is variable within the tumor and its cells. This results from problems in the delivery of drugs (perfusion, interstitial fluid pressure, tissue pH, protein binding, etc.), cellular uptake, efflux, inactivation, and other mechanisms of resistance. In many instances, the agent does not reach the relevant therapeutic targets in the required concentration and for a sufficient time period. In fact, the pharmacokinetic profile of anticancer drugs is characterized by substantial interpatient variability where two- to threefold variation is not uncommon. These issues even gain complexity with simultaneous administration of two or more drugs. Such multiagent regimens with different modes of action might be valuable when each agent kills different tumor cells, which would not become inactivated by the other agent. Depending on variations in actual drug concentration, a fixed combination of two drugs might either show additivity or antagonism in the same tumor cells. Both preclinical and clinical data confirm that rationally designed drug combinations often lead to improved results. Several studies support the superior quantitative cell kill of radiotherapy and suggest that simultaneous application of radio- and chemotherapy is an important measure to increase the efficacy of non-surgical cancer treatment.
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Molls, M., Nieder, C., Belka, C., Norum, J. (2009). Quantitative Cell Kill of Radio- and Chemotherapy. In: Molls, M., Vaupel, P., Nieder, C., Anscher, M. (eds) The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74386-6_10
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