Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression.
OBJECTIVE
Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation.


METHODS
Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later.


RESULTS
Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively).


CONCLUSIONS
The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.
Unger
Keith R
KR
Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908, USA.
Romney
Davis A
DA
Koc
Mehmet
M
Moskaluk
Christopher A
CA
Friel
Charles M
CM
Foley
E F
EF
Rich
Tyvin A
TA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000069287:Capecitabine; D000068579:Celecoxib; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D011720:Pyrazoles; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D000068579:Celecoxib; D005472:Fluorouracil