Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized,controlled trial

PURPOSE: Intravenous fluorouracil and leucovorin for six toeight months is currently a standard adjuvant treatment forStage III colon cancer; however, this regimen is complex,inconvenient, and has a high intolerability. Adjuvant chemotherapiesare claimed for objective response rates withan acceptable safety profile and complexity. We investigatedthe benefits of oral protein-bound polysaccharide Kadded to oral tegafur/uracil on curatively resected Stage IIor III colorectal cancer. METHODS: We prospectively randomized207 patients to treatments of either oral 3.0 gprotein-bound polysaccharide K plus 300 mg tegafur/uracilor 300 mg tegafur/uracil alone for two years following 12mg/m² and 8 mg/m² mitomycin treatment on postoperativeDays 1 and 2, respectively. The primary end points weredisease-free and overall survival, and recurrence rates. RESULTS:Three (1.4 percent) patients were declared ineligible,and three patients did not start treatment. In total, 201patients were analyzed. The three-year, disease-free survivalrate was 80.6 percent (standard error = 3.4 percent) in theprotein-bound polysaccharide K group (P = 0.02) comparedwith 68.7 percent (SE = 5.7 percent) in the controlgroup after a median follow-up of 3.7 years. The estimatedrelative risk of recurrence in the control group was 1.87 (95percent confidence interval, 1.10–3.20) at three years. Thethree-year, overall survival rate was 87.3 percent (standarderror = 2.9 percent) in the protein-bound polysaccharide Kgroup and 80.6 percent (standard error = 4.8 percent) inthe control group (P = 0.24). The three-year, overall survivalrate in 80 pathological TNM Stage III patients was 83.0percent (standard error = 5.2 percent) in the protein-boundpolysaccharide K group and 59.3 percent (standard error =9.5 percent) in the control group (P = 0.02). Protein-boundpolysaccharide K prevented distant metastases (P = 0.05),particularly lung metastases (P = 0.01). The incidence ofadverse effects was minimal, and compliance was good.CONCLUSION: Adjuvant therapy using a combination oforal protein-bound polysaccharide K and tegafur/uracil ishighly effective in preventing the recurrence of colorectalcancer in Stage II or III patients, and increases overallsurvival in pathological TNM Stage III. These results will bea sufficient proof to conduct a larger study to comparetegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/leucovorin.