Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.
OBJECTIVE
To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer.


METHODS
Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival.


RESULTS
All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%.


CONCLUSIONS
UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.
Fernández-Martos
Carlos
C
Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, c/o Professor Beltrán Báguena 8 y 19, 46009 Valencia, Spain. carlosfmartos@mx2.redestb.es
Aparicio
Jorge
J
Bosch
Carles
C
Torregrosa
Marilo
M
Campos
Juan Manuel
JM
Garcera
Salvador
S
Vicent
Jose Maria
JM
Maestu
Inmaculada
I
Climent
Miguel Angel
MA
Mengual
Jose Luis
JL
Tormo
Alejandro
A
Hernandez
Ana
A
Estevan
Rafael
R
Richart
Jose Maria
JM
Viciano
Vicente
V
Uribe
Natalia
N
Campos
Jorge
J
Puchades
Ramon
R
Arlandis
Francisco
F
Almenar
Daniel
D
D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage*; D014498:Uracil / Q000008:administration & dosage*
D005641:Tegafur; D014498:Uracil; D002955:Leucovorin