Abstract P4-11-08: A Pilot Safety and Feasibility Study of Concurrent Capecitabine and External Beam Irradiation in the Adjuvant Treatment of High Risk Early Stage Breast Cancer
Authors: Garwood DP , Spangler A , DeRose PM , Li HC , Osborne C , O‘Shaughnessy J , Tripathy D. 
Published: April 2011

Abstract
Background: Capecitabine (Xeloda ®) is an oral 5-FU pro-drug that is preferentially converted to the active form 5-FU within tumor tissue, offering many of the same benefits of continuous 5-FU infusion with the convenience of oral delivery. In studies of patients receiving chemotherapy with or without radiation therapy, combination therapy has proved more efficacious than either modality alone. If radiation therapy can more effectively eliminate local microscopic residual disease, this will resultin improved local control and may potentially increase overall survival. This phase II study was performed to ascertain the safety and feasibility of capecitabine concurrent with radiation therapy in high risk non-metastatic breast cancer.
Materials and methods: Eligible patients had undergone surgery and chemotherapy for high risk breast cancer, defined for this study as either a T3 or T4 primary tumor, or N2 (≥4 nodes involved) or greater nodal status. Capecitabine was administered at 825 mg/m2 twice daily on days of radiotherapy. The primary endpoint of this study was toxicity, scored using CTCAE v 3.0, evaluated during therapy and in follow-up at intervals up to 12 months. Clinically significant toxicities were defined as skin toxicity or hematological toxicity of grade 3 or greater, or other toxicity felt related to capecitabine of grade 2 or greater. Feasibility was defined as percent of patients completing the course of drug, and the percent of patients completing radiation therapy to a dose of at least 50.4 Gy. Cosmesis was rated by the physician and the patient separately.
Results: 50 women were enrolled in this study; the mean age was 52 (range 33-77). T stage distribution was as follows: T0 4%, T1 16%, T2 50%, T3 18%, and T4 12%. N stage N0 6%, N1 18%, N2 44%, and N3 32%. Mean number of pathologically involved nodes was 8 (range 0-36); 56 % of patients were treated with neoadjuvant chemotherapy prior to definitive surgery, which for 84% was mastectomy. Four patients withdrew prior to starting or within the first week; of the remaining 46 patients, 10 had capecitabine discontinued or dose-reduced, and one patient died during treatment. Those patients who did not receive the full drug dose had on average 3.8 weeks of capecitabine therapy; of the overall 46 patients, 76 % received the intended dose of drug throughout the radiation treatments; 98% of patients received at least 50.4 Gy. Toxicities observed included 7 pts with grade 3 radiation dermatitis, 3 with grade 3 hand-foot syndrome, 1 with grade 4 diarrhea, and 1 with grade 5 cardiac arrest felt possibly related to capecitabine; 2 other grade 3 toxicities (range of motion limitation and bone pain) were felt not related to the study. Mean cosmesis scores at baseline were assessed to be “good” by both patients and physicians; these were stable at 12 months of follow-up. 90 % of patients were alive at 12 months, and 2 (4 %) were observed to suffer local, in-field failure. Discussion: Radiation therapy in combination with capecitabine is a well tolerated adjuvant therapy for patients with high risk breast cancer, with most patients completing all therapy. Controlled studies examining efficacy are warranted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-08.