Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-four patients with advanced gastric cancer were treated with combination chemotherapy employing Tegafur-Uracil (UFT), etoposide, Adriamycin, and Cisplatinum (CDDP) (UFT-EAP therapy). An objective partial response was obtained in 16 patients (47%) and the median duration of remission was 12.2 months. The 50% survival time for all 34 patients was 10 months. Patients with moderately or well differentiated adenocarcinoma responded well (13/19, 68%), while those with undifferentiated adenocarcinoma showed a poor response (3/15, 20%). Six responding patients were noted to have no evidence of viable cancer at the primary site by endoscopic biopsy, and underwent gastrectomies. The resected specimens showed complete disappearances of the primary tumors in four patients. The median survival time for the patients receiving gastrectomies was 24 months. The regimen was very well tolerated, apart from moderate bone marrow suppression. Our results suggest that patients with advanced gastric cancer can be effectively treated with UFT-EAP chemotherapy.
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PMID:Combination chemotherapy with Tegafur. Uracil (UFT), etoposide, adriamycin and cisplatinum (UFT-EAP) for advanced gastric cancer. 796 7

To evaluate the effectiveness of surgical adjuvant chemotherapy, we attempted to determine whether cancer patients were taking oral anticancer agents properly. Tegafur or UFT was administrated orally to patients with gastric or colorectal cancers after surgery for at least a year. There were 19 gastric cancer patients and 18 colorectal cancer patients. Serum levels of Tegafur and 5-FU were measured every three months. Results of the study showed that all the patients took medicine regularly according to the prescription and serum 5-FU levels of most patients (75%) exceeded the minimal effective serum level.
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PMID:[Evaluation of long-term administration of oral anti-cancer agent]. 847 Sep 22

A multi-center collaborative study was conducted in curatively resected gastric cancer patients at Stages II and III to compare oral 5-FU (Group A), oral Tegafur (Group B) and i.v. MMC + oral 5-FU (Group C). From May 1982 to April 1985, 1,012 cases were enrolled at 55 institutions. Some 138 (13.8%) were excluded, and 874 were analyzable. In the analysis of background factors, Group B had more cases with tumor of large diameter and advanced Stage. Adverse effects were relatively mild in all groups, and there was no problem in drug tolerance. Five-year survival rate was 67.6%, 62.4% and 68.6% in Groups A, B and C, respectively, reflecting no significant difference among them. It was 85.0%, 83.0% and 81.1% in Stage II and 52.5%, 51.0% and 59.0% in Stage III of Groups A, B and C, respectively. No significant difference was found, but Stage III of Group C showed a slightly higher survival rate. Supportive clinical study will be required to assess the usefulness of MMC as an introduction therapy. We found no difference in efficacy between 5-FU and Tegafur as maintenance therapy. The life-prolongation effect of fluoropyrimidines in comparison with surgery alone should be studied separately.
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PMID:[Comparative clinical study of adjuvant postoperative chemotherapy (5-FU, Tegafur, 5-FU + MMC) in curatively resected cases of gastric cancer. Study Group on 5-FU Oral Adjuvant Chemotherapy in Gastric Cancer]. 875 4

The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14 days. Based on the promising results obtained with this regimen in patients with advanced colorectal cancer, the Oncopaz group performed several phase II trials using this combination with other drugs to treat advanced gastric, lung, head and neck, and breast cancers. When combined with etoposide in gastric cancer, the regimen was shown to be active and well tolerated. However, when used with cisplatin to treat non-small cell lung cancer, a low response rate and high toxicity precluded its recommendation for further study. The addition of carboplatin in the treatment of head and neck cancer demonstrated moderate activity with low toxicity. In an ongoing trial of advanced breast cancer, preliminary results indicate that the combination of idarubicin, UFT, and leucovorin is active, with moderate, primarily hematologic toxicity. Trials of new combinations are warranted to take advantage of the pharmacokinetic properties and oral bioavailability of UFT and leucovorin.
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PMID:Experience of Oncopaz Cooperative Group with oral fluoropyrimidines in tumors of the stomach, lung, head and neck, and breast. 897 82

We performed preoperative chemotherapy using oral anticancer agents and compared the survival rate with that of the untreated group. The statistical significance of effects in the oral anticancer agent groups was tested by multivariate analysis of the survival rate. The subjects were 488 patients who underwent resection of primary stomach cancer in the Chiba Cancer Center between 1981 and the end of 1991. Patients who were gross type 0 preoperatively, who died in the hospital or who had multiple or double cancer, were excluded. They were divided into two oral anticancer agent groups with 158 patients in the Tegafur group, 163 in the 5-FU group, and 167 patients in the untreated group. In addition to preoperative adjuvant chemotherapy, the age, gender, age, localization, gross type, depth of invasion, histological lymph node metastasis and the old histological stage were analyzed as explanatory variables. In both the Tegafur and 5-FU groups significant differences of p = 0.034 and p = 0.024 were obtained. Factors which had significant effects on survival rate were age (p < 0.0001), histological lymph node metastasis (p < 0.0001), age (p = 0.0001), depth of invasion (p = 0.002), and gross type 4 (p = 0.043). Therefore preoperative administration of oral anticancer agents appeared to have a significant effect on survival rates.
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PMID:[Preoperative adjuvant chemotherapy with oral anticancer agents for stomach cancer]. 923 64

Despite recent progress in surgery and chemotherapy, advanced gastric cancer carries a poor prognosis. Although several antitumor agents have some clinical activity, responses are usually of short duration and fail to improve survival. Combination chemotherapy regimens containing fluorouracil (5-FU) and cisplatin (Platinol) frequently result in higher response rates, but fail to significantly alter the ultimate course of the disease. Tegafur and uracil (UFT) have been extensively studied in gastric cancer in Japan. In responding patients, single-agent therapy results in a 1-year survival of 47%. Studies using combination regimens with UFT are currently performed in Europe, and data from Japan demonstrate that UFT can be safely combined with a variety of other agents. However, the exact contribution of UFT in these combinations will need to be evaluated further. The present review summarizes the use of UFT alone or in combination, as well as in the neoadjuvant and adjuvant settings, in the treatment of patients with advanced gastric cancer.
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PMID:UFT in gastric cancer: current status and future developments. 934 82

Highly effective treatment is required for patients with advanced GI cancer. Returning to the starting point for reconsideration of cancer chemotherapy, with the aim of attaining a therapy (self rescuing concept: SRC) with more potential efficacy and less toxicity than current therapy, we report two kinds of chemotherapy in the present paper. They were set up preclinically using the theory of 5-FU biochemical modulation, and demonstrated their usefulness in clinical practice. S-1 is a newly developed oral anti-cancer drug which is a combination of Tegafur (FT), a prodrug of 5-FU and two modulators (CDHP, an inhibitor of 5-FU degradation and Oxo, a selective inhibitor GI toxicity by 5-FU) at a molar ratio of 1:0.4:1. In combination with CDHP, 5-FU gradually released from FT remained longer in plasma, and consequently had high anti-tumor activity, while the combined Oxo significantly suppressed GI toxicity due to 5-FU. The response rate to S-1 of stomach cancer in a phase II study was 46.5% (60/129). Toxicity at more than G3 was less than 10%. In the combination therapy employing 5-FU by CVI (5-FU: 250-350 mg/body for 24 h, 4-6 wks) and low dose consecutive CDDP, CDDP acts mainly as a modulator of 5-FU (to increase 5-FU sensitivity for tumor by inhibition of intracellular Met incorporation). For this purpose, it was found that daily consecutive administration is required, even at low dose of CDDP (3-5 mg/body/day for 5 days). A high response rate (40-60%) was obtained for advanced GI cancer. Toxicity at more than G3 was less than 10%. On the other hand, the possibility has been suggested that so far as 5-FU is concerned, CVI every other day (500-750 mg/body/day for 3 days) is more favorable than long term CVI, with regard to decreasing GI and myelotoxicities based upon the difference in generation time between normal cell (GI mucous membrane and stem cell) and tumor cell cycles. The possibility is suggested that the above-mentioned chemotherapy can become a standard therapy for GI cancer.
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PMID:[Combination therapy of continuous venous infusion (CVI) of 5-FU and low dose consecutive cisplatin (CDDP), and the new oral anti-cancer drug S-1 for advanced gastro-intestinal cancer]. 1009 42

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg(-1) i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day(-1)) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.
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PMID:The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients. 1120 36

BACKGROUND: Although many trials have been conducted to evaluate the feasibility and effectiveness of adjuvant chemotherapy (ACT) for patients with stomach cancer, the benefits of ACT remain unclear. Moreover, some authors have reported that ACT increased the incidence of second malignancy. The risk of second malignancy was evaluated in patients who underwent treatment for stomach cancer in the past 20 years at Osaka Medical Center for Cancer and Cardiovascular Diseases.METHODS: The study population consisted of 1925 patients who underwent gastrectomies for stomach cancer between the years 1978 and 1992 and who received follow-up examinations to check for second malignancies. They included 1114 patients who underwent surgery only (group A) and 811 who underwent surgery and received chemotherapy (group B). The observed incidence of second malignancy (O) was compared with the expected incidence (E), calculated by the person-year method, using data from the Cancer Registry in Osaka.RESULTS: The average follow-up period was 7.99 years. The total number of patients with a second malignancy was 127 (men, 97; women, 30); 72 patients had the second malignancy in digestive organs; 27 in respiratory organs; and 28 in other organs. The relative risks of a second malignancy in group A and B patients were 1.05 and 1.02 (differences between the two groups were not significant). The relative risks of a second malignancy in patients who received ACT with 5-fluorouracil, Tegafur and Uracil, and FT207 were 0.79, 1.01, and 1.06, respectively (differences between the groups were not significant).CONCLUSION: The risk of second malignancy after chemotherapy for stomach cancer was not high in comparison with the expected incidence. Adjuvant chemotherapy did not increase the risk of a second malignancy.
Gastric Cancer 1999 Dec
PMID:The risk of second malignancy after adjuvant chemotherapy for stomach cancer. 1195 99

Dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP) are metabolic enzymes of fluoropyrimidine. UFT containing uracil (U) and Tegafur is the first reported DPD-inhibitory fluoropyrimidine. To clarify the significance of the enzyme activities, we examined the relationships between the effects and adverse reactions, and DPD and DHP activities in gastric cancer treated with UFT1+cisplatin neoadjuvant chemotherapy. Twenty-five gastric cancer patients were administered UFT at 370 mg/m(2)/day for 21 days and cisplatin at 15 mg/m(2)/day for 2 days. Dihydrouracil (DU) and U levels in the urine and DPD activities in the resected tumors were measured. Chemotherapeutic effects were classified histologically into non-responder and responder groups. The responder group accounted for 48% of the patients. All six patients with high DPD activities (> or = 0.08 nmol/min/ww) belonged to the non-responder group and 11 of 19 patients with low DPD activities (<0.08 nmol/min/ww) belonged to the responder group; the difference was significant (p=0.0435). Adverse reactions to UFT occurred in four patients, all of whom were among the six patients with abnormal DU/U values. The incidence of UFT adverse reactions was estimated at 67%. In conclusion, the measured levels of DPD-related enzyme activities appear to be significant for predicting the effects and adverse reactions to chemotherapy.
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PMID:Dihydropyrimidine dehydrogenase-related enzymes predict efficacy and adverse reactions of UFT1+cisplatin neoadjuvant chemotherapy for gastric cancer. 1198 87


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