title: Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial.
abstract: OBJECTIVE
  Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer.
  
  
  METHODS
  We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-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, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10-3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good.
  
  
  CONCLUSIONS
  Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/leucovorin.
authors.affiliation: Gunma Oncology Study Group (GOSG), Maebashi, Gunma, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohwada
authors.forename: Susumu
authors.initials: S
authors.lastname: Kawate
authors.forename: Toshiroh
authors.initials: T
authors.lastname: Ikeya
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Yokomori
authors.forename: Teruo
authors.initials: T
authors.lastname: Kusaba
authors.forename: Takashi
authors.initials: T
authors.lastname: Roppongi
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010349:Patient Compliance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011509:Proteoglycans / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D011509:Proteoglycans; D005641:Tegafur; C010770:polysaccharide-K; D014498:Uracil