Capecitabine-induced Gastrointestinal Injury Shows a Graft-Versus-Host Disease (GVHD)-like Pattern

Capecitabine is a commonly used oral chemotherapeutic agent. Gastrointestinal (GI) side effects are clinically well-known, however, the histopathologic changes have not been comprehensively studied. This study describes the largest case series (8 patients) characterizing the histopathology of capecitabine-induced GI injury. All patients were adults (median age: 64.5 y, range: 61 to 76 y) and there was gender parity. Patients were receiving treatment for malignancies of the colorectum (n=5), breast (n=1), pancreas (n=1), and appendix (n=1). All had GI symptoms, including 7 with diarrhea and abdominal pain and 1 with melena. Five of 8 (63%) showed graft-versus-host disease (GVHD)-like histologic changes in small intestinal and/or colonic biopsies characterized by crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium, and increased crypt apoptosis. Neuroendocrine cell aggregates were present in 4 of 5 cases. Four of 5 showed patchy prominence in lamina propria eosinophils. One patient receiving concomitant radiation therapy had a small intestinal biopsy showing regenerative changes. Two patients had histologically unremarkable biopsies. On follow-up, capecitabine was discontinued or dose-reduced in all patients. Three of 5 patients with a GVHD-like pattern had clinical improvement, whereas 2 died shortly after biopsy. One with regenerative changes also had radiation dose reduction and improved clinically. Two with unremarkable biopsies improved symptomatically. In summary, capecitabine-related GI injury shows a GVHD-like pattern. Knowledge of this is important to confirm the diagnosis as patients typically improve with dose reduction or discontinuation of the drug.