[Concomitant chemo-radiation treatment of malignant tumors: biological bases]

Concomitant radio-chemotherapy is widely used in the treatment of various localisations of cancer. Numerous interactions are known between ionizing radiation and cytotoxic agents, which in vitro may modify the dose-response relationships. The main interactions are spatial cooperation, independent cell kill, cell synchronization, inhibition of repair of radiation damage, reoxygenation, reduction of the hypoxic fraction and increased apoptosis. Exposure of irradiated cells to cytotoxic agent lead to increase the number of unrepaired double-strand breaks. By this mechanism the action of DNA repair of both therapeutic modalities enhance therapeutic efficiency. The main effects of chemoradiotherapeutic combination in the laboratory are inhibition or antagonism, sub-additive, additive and supra-additive effects. The most important for clinical practice are supra-additive effects, when the cytotoxic effect of the combination is greater than the sum of the effects of radiotherapy alone and that of chemotherapy alone. It is however difficult to extrapolate laboratory and experimental results to clinical practice because the conditions for interaction of chemo- and radiotherapy in vitro are different. Clinical conditions usually are more compatible for additive and sub-additive interactions. The main role of laboratory and experimental investigations is to propose new drug--radiotherapy combination to phase II trials.