Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation.
OBJECTIVE
This study examines the effect of 5-fluorouracil administration during preoperative irradiation on rectal cancer tumor proliferation.


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.


CONCLUSIONS
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 downstaging. New treatment strategies should be aimed at controlled recruitment of quiescent tumor cells at the time of irradiation.
Willett
C G
CG
Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Hagan
M
M
Daley
W
W
Warland
G
G
Shellito
P C
PC
Compton
C C
CC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009367:Neoplasm Staging; D011300:Preoperative Care; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012004:Rectal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*
D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D005472:Fluorouracil