Phase I study of 5-fluorouracil administered by protracted venous infusion, leucovorin, and pelvic radiation therapy

BACKGROUND. This study was designed to assess the toxicity of pelvic radiat ion therapy, 5-fluorouracil (5-FU) administered by protracted venous infusi on, and leucovorin. METHODS. Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administer ed in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg da ily) administered orally and protracted venous infusion of 5-FU. The initia l daily 5-FU dose was 150 mg/m(2). Dose escalations were planned in increme nts of 25 mg/m(2). RESULTS. Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy-related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occu rred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m(2), in 5 of 10 pa tients at a daily 5-FU dose of 175 mg/m(2), and in 5 of 10 patients at a da ily 5-FU dose of 200 mg/m(2). Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 o f the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the las t 7 patients, who were given warfarin orally (1 mg daily) during treatment. CONCLUSIONS. Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5-FU is given daily at a dose of 150 mg/m(2) i s similar to that observed in current chemoradiotherapy regimens for patien ts with rectal carcinoma. This regimen will be considered as a possible inv estigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients. Cancer 1999;86:710-4, (C) 1999 American Cancer Society .