Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation

PURPOSE: This study examines the effect of 5-fluorouracil administration during preoperative irradiation on rectal cancer tumor proliferation. PATIENTS AND METHODS: One hundred and fifty-three patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation with (103 patients) and without (50 patients) concurrent 5-fluorouracil, followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating cell nuclear antigen immunostaining and the number of mitoses per ten high-powered fields. Postirradiation specimens were also assessed for downstaging. RESULTS: Although 5-fluorouracil did not improve downstaging rates, marked decreases in the activity of all three markers of proliferation (mitotic counts, Ki-67, and proliferating cell nuclear antigen immunostaining) were seen in rectal cancers of patients receiving the drug. No significant decreases were noted in patients undergoing irradiation only. CONCLUSION: The addition of 5-fluorouracil to preoperative irradiation resulted in a more complete inactivation of the proliferating population. Frequency of downstaging, however, was unaffected. Thus, the quiescent cell population appears to represent a substantial barrier to further down- staging. New treatment strategies should be aimed at controlled recruitment of quiescent tumor cells at the time of irradiation.