Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer

5-Fluorouracil–based chemotherapy with concurrent radiotherapy (RT) is the standard adjuvant treatment in rectal cancer. A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicities of capecitabine combined with standard RT as adjuvant treatment in patients with rectal cancer. Patients with Stage II–III rectal cancer after surgery were eligible. RT included a total dose of 50.4 Gy in fractions of 1.8 Gy/d, 5 d/wk, for 5.5 weeks. Capecitabine was administered twice daily in escalating doses during the entire period of RT. Dose-limiting toxicity included Grade 4 neutropenia or thrombocytopenia, febrile neutropenia, Grade 3 or greater nonhematologic toxicity, or treatment delay because of unresolved toxicity for >1 week. Thirty-one patients were enrolled at the following dose levels: 1000 mg/m 2/d (3 patients), 1150 mg/m 2/d (4 patients) 1300 mg/m 2/d (6 patients), 1400 mg/m 2/d (6 patients), 1500 mg/m 2/d (3 patients), 1600 mg/m 2/d (3 patients), and 1700 mg/m 2/d (6 patients). Dose-limiting toxicities were observed in 2 patients at 1300 mg/m 2/d (Grade 3 diarrhea), and 2 patients at 1400 mg/m 2/d (skin toxicity in 1 and abdominal pain with fever in 1, resulting in treatment delay), and 3 patients at 1700 mg/m 2/d (2 patients had Grade 3 diarrhea and 1 had hand-foot syndrome). Four patients presented with chronic postradiation colitis. The maximal tolerated dose of capecitabine given concurrently with RT was 1600 mg/m 2/d in this study. This dose is recommended for additional use in Phase II-III studies.