TUMOR-GROWTH AND DRUG-RESISTANCE - LESSONS FROM THE TREATMENT OF HODGKINS-DISEASE (REVIEW)

The resistance of cancer cells to anti-neoplastic agents is a major at tribute of malignancy. Kinetic drug resistance develops as the tumor b urden increases, and is reversible when the cell mass can be reduced. Genetic drug resistance, in contrast, results in the acquisition of po ssibly irreversible resistance by random cell mutation. The latter mec hanism, and one of its corollaries, that rapidly alternating drug regi mens could prevent the advent of new resistant cell lines, have been t he subject of many studies in the last decade. The endpoint to evaluat e in such studies should be an increase in failure-free survival, sinc e such prevention cannot have any influence in the complete remission rates. A review of the clinical trials in Hodgkin's disease suggests t hat failure-free survival rates are in fact improved with the alternat ing schedules. On the other hand, dose-intensification is presently un der study as a means of overcoming kinetic drug resistance, thereby in creasing the complete remission rates, and has recently proved effecti ve in the prolongation of survival in different malignancies. Further understanding of the mechanisms of drug resistance and the prospective appraisal of the combination of both high-dose therapy and alternatin g drug treatments should result in a better outcome, mostly for patien ts with large tumor burdens or other high risk factors.