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

SAN FRANCISCO-Chemoradiationwith capecitabine (Xeloda)appears to be very well tolerated bypatients with locally advanced rectalcancer (LARC) and produces resultsat least comparable to radiotherapyplus continuous infusion (CI)-5-FU,according to a phase II study by researchersfrom M.D. Anderson Can-cer Center, Houston, Texas.The investigators reported theirfindings at the GastrointestinalCancers Symposium, which wascosponsored by the American Societyof Clinical Oncology, AmericanGastroenterological Association,American Society for TherapeuticRadiology and Oncology, and theSociety of Surgical Oncology.Edward H. Lin, MD, NoraJanjan, MD, from the Radiation-Oncology division at M.D. Anderson,and colleagues concluded capecitabineis a convenient, ideal fluoropyrimidinealternative to replaceCI-5-FU for patients with LARC(abstract 251).Study Design and Results
Dr. Lin, Dr. Janjan, and associatesadministered capecitabine 825 mg/m²/day PO twice daily with radiotherapyof 45 Gy administered in 25 fractionsto the pelvis and 52.5 Gy in 30 fractionsto the primary and perirectalnodes of 54 patients with LARC atstage T3 or greater. Postoperatively,chemoradiation with capecitabine wasfollowed by four cycles of adjuvantcapecitabine at 1,250 mg/m²/day POtwice daily for 14 days, with 1 week off.At the time of the symposium, 29patients had been enrolled in the study(median age, 56 years), and 23 patientswere evaluable for toxicitiesduring chemoradiation. The toxicitiesfor both chemoradiation and adjuvantthereapy were mostly grade1/2, with a limited number of cases ofgrade 3 diarrhea.Grade 4 events were very rare andoccurred in one elderly patient (morethan 65 years of age). Of the 20 patientsevaluable for tumor response,13 (65%) have achieved pathologicaldownstaging. Seven patients werewithdrawn from the study. Bothchemoradiation and adjuvant capecitabinewere well tolerated.The trial was based on the observationthat preoperative radiotherapywith CI-5-FU improves sphincterpreservation and produces pathologicalcomplete remissions in patientswith locally advanced rectal cancer.The investigators noted that "capecitabinemimics CI-5-FU via daily oraladministration and is preferentiallyconverted to 5-FU by high intratumorthymidine phosphorylase, which canbe further activated in the tumor byradiotherapy."