CHANGES IN TUMOR PROLIFERATION OF RECTAL-CANCER INDUCED BY PREOPERATIVE 5-FLUOROURACIL AND IRRADIATION

PURPOSE: This study examines the effect of 5-fluorouracil administrati on during preoperative irradiation on rectal cancer tumor proliferatio n. PATIENTS AND METHODS: One hundred and fifty-three patients with loc ally advanced rectal cancer received 45 to 50 Gy of preoperative irrad iation with (103 patients) and without (50 patients) concurrent 5-fluo rouracil, followed by surgery. Pretreatment tumor biopsies and postirr adiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating cell nuclear antigen im munostaining and tile number of mitoses per ten high-powered fields. P ostirradiation specimens were also assessed for downstaging. RESULTS: Although 5-fluorouracil did not improve downstaging rates, marked decr eases in the activity of all three markers of proliferation (mitotic c ounts, Ki-67, and proliferating cell nuclear antigen immunostaining) w ere seen in rectal cancers of patients receiving the drug. No signific ant decreases were noted in patients undergoing irradiation only. CONC LUSION: The addition of 5-fluorouracil to preoperative irradiation res ulted 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 downstaging. New treatment strategics should be aimed at controlled r ecruitment of quiescent tumor cells at the time of irradiation.