[A case of liver metastatic recurrence of gastric cancer effectively treated by combined chemotherapy of CPT-11 and CDDP].

The patient was a 72-year-old female with gastric carcinoma. A liver metastatic recurrence was detected 27 months after operation. Although temporary partial responses were obtained by each effective chemotherapy, which was a combination chemotherapy with 5'-DFUR and TXT, TS-1 and TXL, the metastatic lesion proved refractory to all of them. Then we tried combination chemotherapy consisting of CDDP 30 mg/m2 and CPT-11 60 mg/m2, respectively (day 1 and 15, every 4 weeks). A partial response was achieved and continued for 8.5 months, and her complaints abated and quality of life improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as side effects, they were within a tolerable range and did not interfere with the combination therapy. This regimen appears to be feasible and effective for recurrent gastric carcinoma refractory to other regimens.

Prediction of sensitivity to fluoropyrimidines by metabolic and target enzyme activities in gastric cancer.

BACKGROUND: This study was designed to investigate the role of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) in tumor progression and sensitivity to 5-fluorouracil (5-FU). METHODS: A total of 275 tumor samples from 275 patients with gastric cancer were utilized in this study. TS activity was determined in 130 samples by 5-fluorodeoxyuridine monophosphate binding assay. DPD activity was measured in 140 samples by radioenzymatic assay, and TP protein level was determined in 157 samples by an enzyme-linked immunosorbent assay (ELISA) system. These parameters were compared with several clinicopathologic factors and sensitivity to 5-FU determined by in-vitro ATP assay. The antitumor activities of 5-FU, uracil plus tegafur (UFT), and 1M tegafur--0.4 M 5-chloro-2,4-dihydroxypyridine--1 M potassium oxonate (S-1 [TS-1]) were also compared, using three human gastric cancer xenografts in nude mice. RESULTS: There was no correlation between either TS or TP and sensitivity to 5-FU. However, a weak inverse correlation was found between DPD activity and sensitivity to 5-FU. High DPD activity in tumor resulted in poor prognosis, especially in patients who received 5-FU-based adjuvant chemotherapy. Although TP was significantly correlated with depth of tumor invasion and with lymphatic and venous invasions, TP alone had no impact on survival. On the other hand, TS, as well as peritoneal, hepatic, and lymph node metastases, was selected as an independent prognostic factor in gastric cancer. In the animal model, there was no significant difference in antitumor activities among the drugs in a tumor with low DPD activity. However, S-1 showed superior antitumor activity to 5-FU or UFT in tumors with high DPD activity. CONCLUSION: DPD is considered to be a most important predictive factor of 5-FU sensitivity. The use of DPD inhibitory fluoropyrimidines is strongly recommended for tumors with high DPD activity.

[Combination chemotherapy with intra-perioneal infusion of CDDP and continuous intravenous infusion of 5-FU for peritoneal metastasis in gastric cancer--analysis of long-term survivors].

In order to evaluate the utility of combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU, we performed this therapy in 23 primary gastric cancer patients with peritoneal metastasis. CDDP was administered intraperitoneally at a dose of 70 mg/m2 over 2 hours on day 1, and 5-FU was continuously administered intravenously at a dose of 700 mg/m2 for 5 consecutive days from day 1, respectively. This treatment was given twice. Median survival time with this treatment was 343 days, and the depth of invasion was selected as an independent prognostic factor according to multivariate analysis. Five patients (21.7%) have survived more than 3 years. Major toxicities were less than Grade 2 except for two patients with each anemia (Grade 3) and venous thrombosis (Grade 3), respectively. This regimen appears to be feasible and effective for gastric cancer patients with peritoneal metastases. Long term survival may be obtained in patients without adjacent organ invasion.

Evaluation of the ratio of lymph node metastasis as a prognostic factor in patients with gastric cancer.

BACKGROUND: Lymph node metastasis in patients with gastric cancer is one of the important prognostic factors. However, there is no consensus concerning the best classification for lymph node metastasis as a prognostic factor. So, to evaluate the ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (the ratio of LN meta) as a prognostic factor, we compared the ratio of LN meta with lymph node status according to the Japan Classification of Gastric Carcinoma and the total number of metastatic lymph nodes with multivariate analysis.METHODS: Between 1991 and 1997, a total of 360 patients with primary gastric cancer who underwent gastrectomy with D2 or more extended lymph node dissection were included in this study. Ten kinds of prognostic factors and three types of different classifications for lymph node metastasis were analyzed by multivariate analysis using the Cox regression.RESULTS: The average number of dissected lymph nodes and metastatic lymph nodes were 55.0 (range, 11-184) and 2.6 (range, 0-86), respectively. There were significant differences of the 5-year cumulative survival rates among each group of the ratio of LN meta (0%, 1%-9%, 10%-24%, and more than 25%). Age, tumor size, curability, and the ratio of LN meta were selected as independent prognostic factors by forward stepwise selection. The ratio of LN meta showed the highest hazard ratio by Cox regression.CONCLUSION: The ratio of LN meta appears to be an important prognostic factor and the best classification factor for lymph node metastasis.