The efficacy of preoperative 5-fluorouracil, high-dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.
BACKGROUND
The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5-FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer.


METHODS
Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV-5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins.


RESULTS
The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%).


CONCLUSIONS
These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
B D
BD
Minsky
A M
AM
Cohen
N
N
Kemeny
W E
WE
Enker
D P
DP
Kelsen
L
L
Saltz
J
J
Frankel
D000368:Aged; D001918:Brachytherapy; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D011183:Postoperative Complications; D011292:Premedication; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D012811:Sigmoid Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*
D002955:Leucovorin; D005472:Fluorouracil