Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003).

PURPOSE: Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. METHODS: 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m2/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. RESULTS: The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15-2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97-2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007). CONCLUSION: The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

[A case of diffuse infiltrating carcinoma of large intestine with liver metastases effectively treated with systemic chemotherapy].

We report a case of diffuse infiltrating carcinoma of the large intestine effectively treated by operation and chemotherapy. A 79-year-old woman with bone and liver metastases due to descending colon carcinoma underwent left hemicolectomy and colostomy. Pathological resected specimen findings showed a diffuse infiltrating carcinoma(lymphangiosis type). She re- ceived chemotherapy with 7 courses of mFOLFOX6, 8 courses of mFOLFOX6/bevacizumab(BV), and 5 courses of FOLFIRI/BV after surgical resection. The liver metastases reduced markedly as observed by abdominal CT scan. Twelve months later, DIC caused the death of the patient. Resection with lymphadenectomy and systemic chemotherapy may be effective for treatment of diffuse infiltrating carcinoma of the large intestine.

[A case of liver metastasis of gastric cancer undergoing non-curative operation responding completely to combination therapy of S-1 and CDDP].

We experienced a case with liver metastasis of gastric cancer that disappeared by S-1 administration following non-curative operation. A distal gastrectomy for advanced gastric cancer with liver metastasis was performed on a 71-year-old male. S-1 was administered at 100 mg/body/day for 4 weeks followed by withdrawal for 2 weeks, and CDDP was prescribed at 5 mg/body/day div, for 2 days per a week as 1 course. After one course of treatment, the liver metastatic lesion decreased in size (reduction ratio was 87.4%). For side effect, S-1 100 mg alone was administered beginning with the second course. This lesion became CR after four courses. The adverse events of grade 3 observed during S-1 administration were neutropenia and diarrhea. We changed S-1 to UFT after nine courses, and the patient has now survived 1 year without recurrence after the disappearance of liver metastasis.

Prognostic value of combined analysis of estrogen receptor status and cellular proliferative activity in breast cancer patients with extensive lymph node metastases.

Breast cancer patients with four or more lymph node metastases generally show poor prognosis. However, some can survive for a long period. In this study, we retrospectively evaluated these cases for estrogen receptor status and cell proliferation potential in an attempt to predict patient outcome more accurately. Ninety-two radically operated primary breast cancer patients with four or more lymph node metastases were examined. High PCNA LI and ER-negative status were significantly associated with poor outcome. Then, survival analysis was performed on combination of ER and PCNA LI status, remarkable difference was shown in the prognosis of the patients.

Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis.

BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer.METHODS: One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system.