ABSTRACT
With increasing consideration and use of the combined modality approach in the clinical management of malignant disease, the requirement to define optimal schedules for maximum therapeutic benefit is already appreciated. However, just as the medical oncologist found that moving from single-agent chemotherapy to the use of multiple drugs involved the potential evaluation of many thousands of different combinations and schedules, the introduction of another modality, namely radiotherapy, has served to further compound the problem of optimal treatment selection. The main objective of experimental laboratory studies has been to identify synergistic drug-radiation (DXT) schedules and to define the mechanisms associated with such positive interactions, so as to provide potential leads which might be exploited in the clinic. While laboratory model systems are frequently assumed to provide simple and straightforward means of evaluating drug-DXT interactions, compared to the complexities of testing new modalities in clinical studies, this is of course only relative. Inevitably, as these types of investigations are pursued, the number of variables requiring consideration appears to increase exponentially. It is therefore perhaps not too surprising that while attempting to summarize results of current experimental studies of drug-DXT interactions and to update our earlier reviews,'.' it can certainly be concluded that improved therapeutic results are achievable using this approach. Any precise definition of optimal conditions for the integration of these two modalities for specific drugs or indeed drug combinations, however, still remains beyond our grasp. This chapter aims to highlight the difficulties encountered in interpreting experimental data in this field, to summarize certain general principles which have emerged, and to indicate areas for further development.
