Preoperative Chemoradiation for Rectal Cancer Using Capecitabine and Celecoxib Correlated With Posttreatment Assessment of Thymidylate Synthase and Thymidine Phosphorylase Expression
- Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States)
- Department of Pathology, University of Virginia, Charlottesville, Virginia (United States)
- Department of Surgery, University of Virginia, Charlottesville, Virginia (United States)
Purpose: 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 and Materials: 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.
- OSTI ID:
- 21587642
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 80, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2010.04.016; PII: S0360-3016(10)00589-4; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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CARCINOMAS
COMBINED THERAPY
DISEASE INCIDENCE
POLYMERASE CHAIN REACTION
RECTUM
SURGERY
THYMIDINE
TOXICITY
AZINES
BODY
DIGESTIVE SYSTEM
DISEASES
GASTROINTESTINAL TRACT
GENE AMPLIFICATION
HETEROCYCLIC COMPOUNDS
INTESTINES
LARGE INTESTINE
MEDICINE
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RIBOSIDES
THERAPY