Chemoradiation With Capecitabine Comparable to 5-FU in Locally Advanced Rectal Cancer

SAN FRANCISCO-Chemoradiation with capecitabine(Drug information on capecitabine) (Xeloda) appears to be very well tolerated by patients with locally advanced rectal cancer (LARC) and produces results at least comparable to radiotherapy plus continuous infusion (CI)-5-FU, according to a phase II study by researchers from M.D. Anderson Can- cer Center, Houston, Texas. The investigators reported their findings at the Gastrointestinal Cancers Symposium, which was cosponsored by the American Society of Clinical Oncology, American Gastroenterological Association, American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology. Edward H. Lin, MD, Nora Janjan, MD, from the Radiation- Oncology division at M.D. Anderson, and colleagues concluded capecitabine is a convenient, ideal fluoropyrimidine alternative to replace CI-5-FU for patients with LARC (abstract 251). Study Design and Results
Dr. Lin, Dr. Janjan, and associates administered capecitabine 825 mg/m²/ day PO twice daily with radiotherapy of 45 Gy administered in 25 fractions to the pelvis and 52.5 Gy in 30 fractions to the primary and perirectal nodes of 54 patients with LARC at stage T3 or greater. Postoperatively, chemoradiation with capecitabine was followed by four cycles of adjuvant capecitabine at 1,250 mg/m²/day PO twice daily for 14 days, with 1 week off. At the time of the symposium, 29 patients had been enrolled in the study (median age, 56 years), and 23 patients were evaluable for toxicities during chemoradiation. The toxicities for both chemoradiation and adjuvant thereapy were mostly grade 1/2, with a limited number of cases of grade 3 diarrhea. Grade 4 events were very rare and occurred in one elderly patient (more than 65 years of age). Of the 20 patients evaluable for tumor response, 13 (65%) have achieved pathological downstaging. Seven patients were withdrawn from the study. Both chemoradiation and adjuvant capecitabine were well tolerated. The trial was based on the observation that preoperative radiotherapy with CI-5-FU improves sphincter preservation and produces pathological complete remissions in patients with locally advanced rectal cancer. The investigators noted that "capecitabine mimics CI-5-FU via daily oral administration and is preferentially converted to 5-FU by high intratumor thymidine phosphorylase, which can be further activated in the tumor by radiotherapy."