Phase 1 Study of Neoadjuvant Short-Course Radiation Therapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer

PURPOSE: To assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer. METHODS AND MATERIALS: Patients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX. To mitigate the potential added toxicity from concurrent 5-FU, intensity modulated RT was used. Using the continual reassessment method, the dose of 5-FU was escalated from 100 to a maximum-tolerated dose of 200 mg/m(2)/d. RESULTS: Fourteen patients were accrued. All patients completed continuous infusion 5-FU and short-course RT and the 5-FU dose was safely escalated to 200 mg/m(2)/d with no dose-limiting toxicity. Thirteen patients received the neoadjuvant mFOLFOX, and only 1 patient went straight to surgery after chemoradiation. Clinical response was 21% complete, 63% partial, 14% stable disease, and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 64% partial response and 14% stable disease. No patients had pathologic progression. The most common grade 3 and 4 toxicities were cytopenias. The most common grade 1 and 2 toxicities were cytopenia, fatigue, diarrhea, and nausea. CONCLUSIONS: Our findings suggest that concurrent chemotherapy with neoadjuvant short-course RT is feasible and can be safely given with concurrent continuous infusion 5-FU. This works adds to the growing evidence that short-course RT is not only equivalent to long-course RT, but also may provide additional benefits, such as allowing for a transition to full dose systemic therapy in the neoadjuvant setting, selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic RT.