A phase II trial of pre-operative capecitabine and concurrent radiation for locally advanced rectal cancer

Abstract

3771 Background: Concurrent 5-FU-based chemotherapy and radiation therapy (RT) have an established role in the pre-operative management of locally advanced rectal cancer. Pathologic complete response (CR) rates have been reported from 10% to 50%. We sought to examine the efficacy and toxicity of capecitabine, an oral fluoropyrimidine prodrug, with concurrent RT for this disease. Methods: Between 1/02 and 12/03, 22 patients were enrolled and clinically staged by endorectal US, and CT or MRI. Patients with T3, T4, or lymph node (LN) positive adenocarcinoma of the rectum were eligible. RT was administered in 1.8 Gy fractions to a total dose of 50.4 Gy. Capecitabine (1650 mg/m2/d) was administered by mouth divided in two daily doses Monday through Friday during the entire course of radiation. Surgery was performed 6 to 8 weeks following completion of radiation. Four to 6 weeks after surgery an adjuvant course of capecitabine (2500 mg/m2/d) was administered for 14 days of a 3 week cycles for a total of 6 cycles. Results: Thus far, 22 patients have been enrolled in this study. Eighteen patients were analyzed for toxicity and response. Stage of disease was: 11 T3N0M0, 6 T3N1M0, and 1 T3N2M0. Median age was 55. Pathologic CR was observed in 3 patients (17%), however a near pathologic CR was noted in 2 (11%) additional patients that had only microscopic foci. Primary tumor and LN downstaging occurred in 5 of 18 (28%) and 6 of 7 (86)% patients, respectively. Overall downstaging of tumors (including LN+ disease) occurred in 9/18 (50)% of patients. Of 8 patients who had primary tumors ≤6 cm from the anal verge, sphincter-preserving therapy was performed in 3 (38%) patients. No grade III or IV hematologic toxicity was noted. Two patients (11%) experienced Grade III diarrhea, and 2 patients had grade II diarrhea. Grade III hand foot syndrome was observed in 2 patients. Grade III cardiac toxicity was noted in 2 patients. Conclusions: Concurrent capecitabine and RT is a well-tolerated, safe, and effective treatment for locally advanced operable rectal cancer. This regimen was highly active, leading to frequent tumor downstaging and sphincter preservation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche