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)

KW-2083 [7-n-(p-hydroxyphenyl)-mitomycin C] is a new mitomycin C (MMC) derivative. Its myelotoxicity was compared with that of MMC by using colony-forming unit-spleen (CFU-S) from the femurs of C57BL/6 mice. As a result, it was estimated that the intensity of myelotoxicity of MMC was four times greater than that of KW-2083. Based on this data, a clinical trial of KW-2083 was conducted in 24 cases with various types of advanced solid tumors. KW-2083 was administered by i.v. injection at a dose of 40 mg/body every week. Out of 15 evaluable cases, a case of ovarian cancer showed a partial response. One case of each of ovarian cancer and gastric cancer showed minor response. However, as with mitomycin C, the dose-limiting toxicity of KW-2083 was leukopenia and thrombocytopenia. Other toxicities encountered were nausea, vomiting, anorexia, phlebitis and hepatic dysfunction. There were no cases with renal toxicity. Plasma concentration of KW-2083 was bioassayed in 3 cases who received 40 mg/body as an i.v. bolus injection. Plasma concentration-time curves fitted to a one-compartment model and half-life values averaged 27.6 min. The effective and low toxic dose schedules of KW-2083 should be investigated further.
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PMID:[A clinical trial of a new mitomycin C derivative, KW-2083 (7-N-(p-hydroxyphenyl)-mitomycin C)]. 403 9

Forty patients with hepatoma and metastatic tumors of liver were treated with rapid arterial infusion administered simultaneously using 30-40 mg of adriamycin and 10-20 mg of mitomycin C into the hepatic artery by Seldinger catheter. They were 16 patients with breast cancer, 21 with gastrointestinal tumors including hepatoma; 6, gastric cancer; 5, colon cancer; 7, gallbladder cancer; 2, pancreas cancer; 1, and three with other malignancies, respectively. Partial responses were obtained in 14 of 40 patients (35%). The response rate in patients with breast cancer was 44% (7/16), while it was 29% (6/21) with gastrointestinal tumors. The median duration of response was relatively short, being 3.5 months in the former patients and 2.3 months in the latter patients. The median duration of survival was 4.0+ months. The results indicate that this arterial infusion therapy is one of the useful treatments in the management of malignant tumors of the liver. Leukopenia less than 4 x 10(3)/cmm was seen in 63%, while thrombocytopenia less than 100 x 10(3)/cmm in 38%, and decreased hemoglobin value of more than 2 g/dl in 13%, which were quite tolerable. Gastrointestinal symptoms and hair loss were milder than those from systemic chemotherapy. Renal toxicity was seen in three patients, and two patients died of renal failure, thus the renal toxicity, which may be related to contrast media as well as anticancer agents, should be carefully prevented by proper hydration.
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PMID:[Arterial infusion of combination chemotherapy using adriamycin and mitomycin C for hepatoma and metastatic tumors of the liver]. 630 77

In order to establish a standard chemotherapy for advanced gastric cancer, a randomized controlled trial to compare clinical efficacy of two regimens consisting of ADM, 40 mg/m2 q. 3W plus 5-FUDS, 4 mg/kg daily (AF) versus MMC, 10 mg/m2 q. 3W plus 5-FUDS, 4 mg/kg daily (MF) for advanced gastric cancer was performed by a cooperative group involving 82 institutions throughout Japan and the following results were obtained. 1. Of 82 evaluable patients with measurable lesions, partial responses were seen in 8 cases (17.4%) out of 46 patients on AF arm and in 4 cases (11.1%) out of 36 patients on MF arm. 2. Of 18 patients receiving cross over from AF arm to MF arm, partial responses were seen in 2 cases, while there was no responder in 11 patients receiving cross over from MF arm to AF arm. 3. The median survival time of a total of 119 patients treated with AF was 157 days while that of 107 patients with MF was 139 days. This difference was not statistically significant. 4. Patients treated with AF had higher incidence of epilation and clinical cardiac symptoms, while thrombocytopenia was more profound in MF arm.
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PMID:[Chemotherapy for advanced stomach cancer -- a controlled study of AF and MF]. 635

Thirty patients with advanced gastric cancer were treated with a combination chemotherapy consisting of adriamycin 20-30 mg/m2 iv day 1 q3wks, mitomycin C 2.7-4 mg/m2 iv day 1 weekly, and ftorafur 267 mg/m2 po b.i.d. daily. Five (28%) of 18 patients with measurable lesions achieved partial responses with a median duration of 2 months ranging 1.5 to 8 months. The median survival time from initiation of the chemotherapy was 4 months in responders, and 5 months in non-responders, respectively. The response rate did not correlate with the various baseline parameters including initial performance status, resectability of the primary tumor, histologic differentiation of the tumor, and prior chemotherapy. Gastrointestinal and hematologic toxicities were mild and well manageable. Cumulative thrombocytopenia and renal damage probably due to mitomycin C, were seen in 5(17%) and 2(7%) patients, respectively. Clinical cardiotoxicity induced by adriamycin was observed in one patient. The result indicated that the enhancement of antitumor effect with a combination of adriamycin, mitomycin C, and ftorafur for advanced gastric cancer was not significantly remarkable as expected. Thus, further study will be required for obtaining more favorable result.
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PMID:[Combination chemotherapy of advanced gastric cancer with adriamycin, mitomycin C, and ftorafur]. 640 98

A controlled clinical trial of surgical adjuvant immunochemotherapy of gastric cancer was started in July, 1974 involving twelve institutes (Chairman; T. Kondo) in Japan. Patients with gastric cancer undergone curative resection were eligible. These patients were divided into 3 groups; Group A, mitomycin C (MMC) + 5-fluorouracil (5-FU): Group B, MMC + 5-FU + PSK or MMC + 5-FU + OK-432; and Group C, surgery alone. Of 1412 patients accumulated up to December 1977, 848 cases were evaluable: Group A-264 cases, group B-290 and group C-294. Side effects such as leukopenia, thrombopenia, elevated GOT and GPT, albuminuria and digestive disorders, were observed in 54 cases (20.5%) of group A and in 59 cases (20.3%) of group B. The 3-year survival rates of total cases were 79.2% with group A, 77.0% with group B and 85.2% with group C. The 2-year survival rates of histological stage II cases were 93.4% with group A, 90.5% with group B and 80.7% with group C. The difference in survival rate between A and C (12.7%) was statistically significant (p less than 0.05). The efficacy was not related to the histological type of gastric cancer. Adjuvant immunochemotherapy using OK-432 was significantly effective on a 1-year survival rate of stage IV gastric cancer.
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PMID:[Cooperative studies on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer]. 642 Dec 43

Chlorozotocin is a glucose-substituted chloroethyl nitrosourea with pharmacologic properties suggesting it is a relatively nonmyelosuppressive cancer chemotherapy drug. Preclinical studies have shown that this drug possesses approximately twice the in vitro alkylating activity of the chloroethyl nitrosoureas BCNU and CCNU. In the L1210 leukemia system, chlorozotocin has curative activity at doses that result in minimal bone marrow toxicity. In vitro studies of human bond marrow stem cells have shown that chlorozotocin is relatively sparing of these cells compared to BCNU. Phase I and phase II trials in man have been performed that show that chlorozotocin's dose-limiting toxicity is thrombocytopenia at doses greater than 120 mg/m2. In the phase II trial, 16% of patients with colon cancer and 20% of patients with malignant melanoma evidenced objective regression of disease. Chlorozotocin is now undergoing phase II evaluation in combination chemotherapy trials in colon and stomach cancer.
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PMID:Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity. 644 66

A phase II study of MCNU tablets in gastrointestinal cancer was carried out by the Hanshin MCNU cooperative study group involving 21 institutions. The selection of patients and evaluation of tumor response were based on the Criteria for the Evaluation of tumor Response by Chemotherapy in Solid Tumor Patients by Koyama and Saito. Of 67 patients who were entered into the study, 46 patients were evaluable, and comprised of 27 cases of gastric cancer, 13 of colorectal cancer, 2 hepatoma, and 4 patients suffering from other typas of gastrointestinal cancer. MCNU was administered orally at a dose of 50 mg/body/day for 4-6 days consecutive every 6-8 weeks. Only one partial response was obtained among the rectal cancer patients, with a response rate of 2.3% (1/43) in evaluable patients. Minor responses were obtained in 3 patients including 2 of gastric cancer with liver metastasis and 1 colon cancer with liver metastasis. Major side effects were marrow suppression and gastrointestinal symptoms. The former consisted of mainly leukopenia (15 patients, 30.0%), thrombocytopenia (20 patients, 40.0%), and oligochromaemia (10 patients, 20.0%). The latter consisted of mainly nausea and vomiting (5 patients, 10.0%).
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PMID:[A phase II study of ranomustine (MCNU) tablets in patients with gastrointestinal cancer--by cooperative study group]. 649

A phase II study of KW 2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C] was carried out in 14 cases of stomach cancer, 5 of lung cancer, 5 of colon cancer and 5 other types of cancer. KW 2083 was intravenously injected at a dose of 40 mg/body weekly in 26 cases. Among 23 evaluable cases, partial response was obtained in 6 cases (26%). The PR cases were 4 of stomach cancer and 2 of lung cancer, the former being all undifferentiated adenocarcinoma. Regarding hematologic toxicities, thrombocytopenia was the most principal toxicity and an important weak point of KW 2083. Thrombocytopenia (less than 75,000/mm3) was observed in 13 cases (50%). Recovery took about 4 weeks, but by that time 3 cases had still not recovered to 75,000/mm3. leukocytopenia (less than 3,000/mm3) was observed in 17 cases (65%). Concerning gastrointestinal symptoms, anorexia occurred in 11 cases (42%), nausea and vomiting in 11 cases (42%), diarrhea in 1 case and stomatitis in 1 case. T1/2 (beta-phase) of KW 2083 was half that of Mitomycin C.
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PMID:[Phase II study of KW 2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with various cancers]. 650 15

In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.
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PMID:High-dose MTX/5-FU and adriamycin for gastric cancer. 660 23

Eighteen patients with gastric cancer in Stage IV who had failed combination chemotherapy were treated with cis-dichlorodiammineplatinum as a single agent. Objective response was observed in four patients (22%), and another two had stable disease lasting 114 and 234 days, respectively. The median duration of the response was 150 days (range, 92-186). Gastrointestinal toxicity occurred in all the patients, but leukopenia and thrombocytopenia was the major complication in patients who had been heavily pretreated. The response rate found in this study shows that cis-platinum is an active drug in gastric cancer.
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PMID:Phase II clinical trial of cis-dichlorodiammineplatinum in gastric cancer. 668 84


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