A phase II pilot study of high-dose 24-hour continuous infusion of 5-FU and leucovorin and low-dose PALA for patients with colorectal cancer: A Southwest Oncology Group study

Purpose: The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced colorectal cancer. Patients and methods: Patients were required to have histologically confirmed colorectal cancer with distant metastases. The treatment regimen consisted of 5-FU 2600 mg/m ² as a 24-hours continuous infusion given once a week, concurrently with leucovorin (LV) at 500 mg/m² as a 24-hour continuous infusion. PALA was administered 24 hours prior to 5-FU/LV at a dose of 250 mg/m ² iv over 15 minutes weekly. Patients were continued on the assigned treatment regimen until progression of disease, unacceptable toxicity, or the patient declined further therapy. Results: This study accrued 28 patients and all were eligible and evaluable for toxicity. Four patients had inadequate assessment of response and are considered non-responders. There was one complete response and five partial responses for an overall response rate of 6/28 or 21% (95% confidence interval 8-41%). Estimated median survival was 17.4 months (95% confidence interval 13.3-20.5 months). One patient died of a treatment related infection. This patient also had grade 4 diarrhea and vomiting. Conclusion: The combination of 5-FU, leucovorin, and PALA in the doses and schedule used here, produces a response rate similar to other modulated schedules of 5-FU with similar survival and toxicity profiles.