What do we know about the mechanisms of the time factor in oncological therapy?

Background: Experimental studies and prospective randomized clinical trials have demonstrated a detrimental effect of prolongation of overall treatment time on local tumor control. Methods: In a brief review of the literature, possible mechanisms of the time factor are discussed. Results and Conclusions: The mechanisms of the time factor in cancer treatment are complex and, at present, not fully understood. In experimental tumors, rapid proliferation of clonogenic cells during fractionated irradiation and treatment gaps has been determined as a major cause of the time factor in radiotherapy. Also, chemotherapy can stimulate repopulation of experimental tumors by clonogenic cells. Besides repopulation of clonogenic tumor cells, other factors such as the deterioration of the tumor vasculature with increasing tumor hypoxia might contribute to the time factor. (orig.)