Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114.
OBJECTIVE
The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure.


METHODS
All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy.


RESULTS
One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females.


CONCLUSIONS
There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.
Tepper
J E
JE
Department of Radiation Oncology, University of North Carolina, Chapel Hill 27599-7512, USA. tepper@radonc.unc.edu
O'Connell
M
M
Niedzwiecki
D
D
Hollis
D R
DR
Benson
A B
AB
Cummings
B
B
Gunderson
L L
LL
Macdonald
J S
JS
Martenson
J A
JA
Mayer
R J
RJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil