BACKGROUND: Building on results from Southwest Oncology Group trial 8905, this trial was designed to compare low-dose continuous infusion (LDCI) of 5-fluorouracil (5-FU) versus intermittent high-dose infusion (HDI) of 5-FU in disseminated colorectal cancer (CRC) for evidence of survival advantage based on dose intensity. A companion trial was funded to assess molecular parameters associated with fluoropyrimidine response or resistance and toxicity from these treatments. PATIENTS AND METHODS: Eligibility included histologic diagnosis of disseminated CRC, measurable or evaluable disease, no previous therapy for metastatic disease, performance status of 0-2, and adequate renal, hepatic, cardiac, and hematologic function. Stratification factors were measurable versus evaluable disease, performance status of 0/1 versus 2, presence versus absence of adjuvant therapy, and presence versus absence of previous surgery and enrollment on the companion trial. Patients were randomized to receive (1) LDCI 5-FU 300 mg/m(2) per day for 28 days every 5 weeks or (2) HDI 5-FU 2,600 mg/m(2) for 24 hours each week. RESULTS: Between April 1995 and May 1999, 730 patients were accrued (LDCI arm, n = 360; HDI arm, n = 370). Of these, 708 eligible patients were assessable for survival and 690 for toxicity. Median survival for both groups was 13 months. Toxicity was mild; < 10% of patients in both arms had grade > 4 events. There were 8 study-related deaths (1%). Less than 10% of patients were enrolled in the companion trial. CONCLUSIONS: Increasing 5-FU dose intensity yields no survival advantage beyond that achieved with LDCI 5-FU. This study confirms the favorable toxicity profile of infusional 5-FU. Because no preferential benefit was observed for either infusion schedule, the more convenient weekly schedule should be considered for 5-FU-based combination regimens for disseminated CRC.
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