Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic beta-catenin activation.

PURPOSE: Protein-bound polysaccharide K is an immunotherapeutic agent that promotes apoptosis by inhibiting nuclear factor-kappaB activation in cancer cells. We previously showed that oncogenic beta-catenin activates nuclear factor-kappaB and inhibits apoptosis by up-regulating beta-transducin repeat-containing protein. We investigated whether the activation state of beta-catenin in the primary tumor is associated with differences in survival rates of patients with colon cancer undergoing immunochemotherapy with 5-fluorouracil plus polysaccharide K vs. chemotherapy with 5-fluorouracil alone. METHODS: We assessed the activation states of beta-catenin and nuclear factor-kappaB in the primary tumors of 202 colon cancer patients, and analyzed the data in terms of the clinicopathologic characteristics and survival of patients undergoing the two forms of adjuvant therapy. RESULTS: We found two distinct patterns of nuclear accumulation of activated beta-catenin in the tumor cells: diffuse nuclear accumulation in 89 cases (44 percent) and selective nuclear accumulation at the tumor invasion front in 18 cases (9 percent). Nuclear factor-kappaB activation was found in 64 cases (32 percent). In patients with diffuse nuclear accumulation-type beta-catenin activation, immunochemotherapy significantly improved recurrence-free survival, cancer death survival, and overall survival rates compared with patients receiving chemotherapy alone. No survival benefit was found in cases with nuclear accumulation at the tumor invasion front-type beta-catenin activation or no activation. Similarly, immunochemotherapy favored the survival of patients with nuclear factor-kappaB activation. Multivariate analysis established the TNM stage and administration of polysaccharide K as independent prognostic factors in the patients with diffuse nuclear accumulation-type beta-catenin activation. CONCLUSIONS: The presence of diffuse nuclear accumulation-type beta-catenin activation identifies patients with colon cancer who respond better to immunotherapy with polysaccharide K.

A new method of thermo-chemotherapy using a stent for patients with esophageal cancer.

PURPOSE: Many patients with advanced esophageal cancer have a stent inserted in the esophagus, but very little else can be done. We devised a new method of delivering thermotherapy using an implant heating system (IHS) with a metallic stent. To our knowledge, there are no other reports of thermotherapy using metallic stents. We report our clinical results of treating patients with this new technique. METHODS: A metallic stent was placed in the esophagus and heated for thermotherapy. This was combined with simultaneous chemotherapy in 13 patients and radio-chemotherapy in 5 patients. Each thermotherapy session consisted of heating the stent to 50 degrees C for 10 min. These 18 patients received a collective 52 sessions of thermotherapy. The tumor was excised after this treatment in 5 of these 18 patients. RESULTS: We evaluated 17 of the 18 patients, after the exclusion of 1 patient who underwent radio-chemotherapy before placement of the stent. There was 1 complete response (CR) and 12 partial responses (PR), accounting for 76%. The patient with a CR had no residual cancer cells detected by pathologic examination after surgical resection. Thermotherapy proved effective in 8 (89%) of 9 patients who received this treatment at least three times. It was effective in all (100%) patients who underwent concomitant radio-chemotherapy. CONCLUSIONS: Our results show that thermotherapy using a stent can improve the effectiveness of combination therapy, suppress local tumor growth, and enhance quality of life over a long period.

An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer.

BACKGROUND: Oral carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard. METHODS: We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of oral carmofur for curatively resected colon cancer in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, carmofur as adjuvant chemotherapy compared with surgery-alone, 5 years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in carmofur and surgery-alone group. Oral carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95% confidence interval (CI) = 0.68-0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95% CI = 0.65-0.91; P = 0.003). CONCLUSIONS: This individual patient-based meta-analysis demonstrated that oral carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers.

Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up.

BACKGROUND AND AIMS: The efficacy of a biological response modifier polysaccharide K in adjuvant immunochemotherapy was evaluated in primary colon cancer patients with macroscopic Dukes' C after curative resection. PATIENTS AND METHODS: Employing the minimization method using three factors (lymph node metastases, preoperative serum CEA level, and institution), 446 patients were allocated into groups P and C. Group P received immunochemotherapy, oral PSK (3 g per day) followed by oral 5-FU (200 mg/body per day), while group C received only intermittent chemotherapy, oral 5-FU (200 mg per day) followed by 4-week rest. Both groups received ten courses. RESULTS: Survival for cancer death was significantly higher in group P than in group C, but there was no difference in 7-year disease-free survival or overall survival had. CONCLUSION: Repeated alternating administration with PSK followed by 5-FU can improve survival for cancer death.

Modification of adriamycin pharmacokinetics by direct electric current in rats.

Adriamycin (ADR, doxorubicin), a drug having cardiotoxicity, is electrically charged as a cation in blood. We therefore investigated whether iontophoresis caused by direct electric current (DC; 50 microA, 90 min) would cause systemic modification of ADR pharmacokinetics. Cathode and anode were placed into a right kidney and muscles of the abdominal wall, respectively, in six Donryu rats. Urinary excretion of ADR, as measured by catheterizing into the right kidney, was significantly higher in the DC group than in the controls (p < 0.05). Both plasmic and renal ADR clearances were significantly higher in the DC group (p<0.005 and p<0.001, respectively). Tissue ADR concentrations were significantly lower in the DC group (heart: p<0.003; liver and lung: both p<0.05). These results suggest that electric therapy might potentially induce modification of ADR pharmacokinetics by iontophoresis, and that the therapy might effectively change ADR concentration both locally and systemically.