Efficacy of continuous venous infusion of fluorouracil and consecutive low-dose cisplatin as adjuvant treatment in resectable colorectal cancer: a prospectively randomized trial

Abstract

3696 Background: Low-dose cisplatin (CDDP) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin. On the other hand, in Japan, adjuvant therapy using oral fluoropyrimidines after curative resection of a colorectal tumor has been achieved since the 1980s. For many years, oral fluoropyrimidines have been frequently used in the adjuvant setting for curatively resected colorectal cancer. We performed a randomized trial to compare the efficacy and toxicity of a continuous venous infusion of 5-FU plus low-dose CDDP (low-dose FP) treatment followed by oral 5-FU with those of oral 5-FU alone in Dukes’ B and C colorectal cancer in the adjuvant setting. Methods: One hundred and eighty-two patients were enrolled. Patients were randomly assigned to receive a treatment of low-dose FP (5-FU; 320 mg/m2, days 1–21, CDDP; 3.5 mg/m2 daily for 21 days) followed by oral 5-FU (200 mg/day daily for 2 years) or an oral 5-FU treatment (200 mg/day daily for 2 years) exclusively. Results: The 5-year disease-free survival (DFS) and the 5-year overall survival (OS) indicated no significant difference between the two groups. By stratified analysis, in the colon cancer patients, the DFS in patients receiving low-dose FP treatment was significantly increased: 93.5% in the FP treatment group as compared with 76.9% in the oral 5-FU group (p=0.024). However, in the rectal cancer patients, there was no difference between the oral 5-FU group and the low-dose FP treatment group (5-year DFS; 60.0% vs. 59.4%, p=0.887). After covariate adjustment, the low-dose FP treatment improved the hazard risk of relapse in the colon cancer patients (HR=0.301, 95%CI. 0.081–1.115, p=0.072). Grade 3–4 toxicities were low in the two groups. Conclusions: In the overall analysis, this study failed to show improvement in DFS or in OS. However, the subgroup with colon tumors treated with low-dose FP followed by oral 5-FU seemed to have a DFS advantage in comparison with the oral 5-FU treatment. Low-dose FP has mild toxicities and is a tolerable regimen. These data suggest that low-dose FP followed by oral 5-FU is a feasible regimen for cancer patients with a resected colon cancer patients. No significant financial relationships to disclose.