Combined modality treatment for primary tumor.

The combination of radiotherapy and chemotherapy is aimed at improving local control and eradicating distant metastases by using cytostatic drugs as radiosensitizing or independent cell-killing agents. This approach has been successful in some areas but has failed in a large number of trials. The failure can be attributed to biologic and clinical factors; the low drug uptake in the tumor is one of the most limiting factors. New approaches should therefore include the improvement of drug targeting and the use of predictive assays; these efforts should proceed with the performance of pharmacokinetic studies and experiments testing the effects of combined treatment on tumors and normal tissues. Pharmacokinetic studies should include measurement of the intracellular drug uptake, preferably at the target. This is now possible for cisplatin; DNA adducts induced by this drug can now be measured with an immunocytochemical technique. The experimental animal studies should include testing of the effects of fractionated irradiation with drugs on tumors and on early- and late-responding normal tissues.