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In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.
Budd et al. (Sun,) studied this question.