Keynote address: integration of cytostatic agents and radiation therapy: a different approach to "proliferating" human tumors.

Failure to achieve local and regional tumor control with radiation therapy remains a significant problem for a number of anatomic sites and can have a negative impact upon survival. There is emerging clinical and laboratory evidence that proliferation of tumor clonogens during the course of radiation treatment significantly impairs local control. Recent in situ studies suggest that as many as half of all human carcinomas have the potential to double their cell number in 5 or fewer days. Thus, cells that survive the initial treatments might rapidly repopulate a tumor, resulting in local failure. One potential clinical approach to reduce the impact of tumor cell repopulation during treatment would be to administer biological or chemical modifiers to slow or inhibit tumor proliferation. Examples of these cytostatic modifiers which are available for clinical testing now, or in the near future, include hormones, anti-hormones, growth factors, growth factor antagonists and other biologicals (e.g., interferons). Clinical alteration of the proliferative status of tumors could influence tumor control by reducing the impact of tumor cell proliferation during therapy, by modifying tumor cell radiosensitivity, or by favourably altering both. To appreciate the magnitude and the cumulative effect of these factors, newer technologies and experimental model systems need to be exploited in investigating correlations between proliferation and tumor control and between proliferative status and radiosensitivity. The design of future clinical trials using cytostatic agents and radiotherapy will rely heavily upon such basic information.