[Biological basis for concomitant chemoradiotherapy in carcinomas]

Clinical trials carried out during the last decade have shown that chemo-radiotherapeutic combinations can be used to improve the treatment of locally advanced carcinomas in a range of localisations. A small number of drugs only, among which platinum salts are the most frequently used, was selected on the basis of randomized trials. The rationale for these combinations relies on spatial cooperation for the control of metastases and on interaction at the level of the primary tumour. Such interaction may take place at the molecular level, with altered DNA repair or modification of the lesions induced by drugs or radiation; at the cellular level, notably through cytokinetic cooperation arising from differential sensitivity of the various compartments of the cell cycle to drug or radiation; and at the tissular level including reoxygenation, increased drug uptake or inhibition of repopulation or angiogenesis. Further improvements aiming at an increased therapeutic index, should come from studies on the mode of action of drugs and on the mechanisms of acute toxicity of drugs and radiation.