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)

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

In a series of 46 patients with localized gastric cancer treated at Massachusetts General Hospital, problems with excessive acute or chronic toxicity due to combination treatment with irradiation (XRT) and chemotherapy (CT) were not seen. Forty of the 46 received combined treatment with 2 regimens: 1) Irradiation plus concomitant 3 days of 5-FU followed by maintenance 5-FU or combined drugs--26 patients; 2) In the other 14 patients, the sequence of irradiation and chemotherapy was altered. A single course of combined drug chemotherapy was given prior to irradiation and 5-6 additional courses were administered after completion of XRT (CT-XRT-CT). The drug combination was initially 5-FU-BCNU but this was changed to FAM (5-FU, Adriamycin, Mitomycin C). Irradiation was delivered to tightly contoured portals using shaped blocks to spare as much small bowel, kidney and marrow as possible while giving 4500-5200 rad in 25 to 29 fractions over 5 to 6 weeks. In this series, there were no cases of septicemia or any deaths related to treatment. A 3 year survival rate of about 20% was achieved for the total group of patients and 43% in the group with resection but at high risk for later failure. Our inability to improve these numbers is undoubtedly a result of dose limitations with external beam irradiation combined with a systemic failure problem. When irradiation is combined with surgical resection of all or a majority of tumor, both survival and local control appear to be better than in the unresected patient group. Only 4 of 29 patients (14%) with curative resection, or resection but residual disease, had later evidence of failure within the irradiation field as opposed to 6 of 9 or 66% in the group with unresectable disease.
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PMID:Combined modality treatment of gastric cancer. 668 72

Gastric cancer is the most chemotherapy-responsive adenocarcinoma of the major gastrointestinal sites. For patients with advanced disease, the response rates and survival achieved with recently designed Adriamycin-based regimens represent an improvement over the past use of 5-fluourouracil alone or combined with a chloroethylnitrosourea. Effective palliative treatment can be administered in an out-patient setting without the necessity of producing severe or life-threatening toxicity. Nevertheless, response durations are finite, as is patient survival. It is essential that Phase II trials of new drugs be continued in an attempt to identify agents with greater therapeutic activity for this disease. For the locally unresectable stage, combined modality therapy incorporating palliative resection of the primary tumor, regional radiation therapy and chemotherapy, has provided long-term disease-free survival for 15--25% of all patients. The most promising aspect of current clinical investigation is the application of the Adriamycin-based drug combinations in controlled trials of surgical adjuvant therapy.
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PMID:Current management of advanced and locally unresectable gastric carcinoma. 675 66

This report summarizes the results of a randomized multi-institutional clinical trial in advanced gastric carcinoma comparing four combination chemotherapy regimens: 5-FU, Adriamycin + mitomycin C (FAMi); 5-FU, Adriamycin + methyl-CCNU (FAMe); 6-FU, ICRF-159 + methyl-CCNU (FIMe); and 5-FU + methyl-CCNU (FMe). One-hundred-eight-one evaluable patients received chemotherapy. These objective tumor response rates were observed among the 59 patients with measurable indicator lesions: FAMi, 3/12 (25%); FAMe3, 3/10 (30%); FIMe, 4/19 (21%); FMe, 1/18 (6%). The survival distributions for the four treatment groups were significantly different (P less than or equal to 0.05), with these median survivals observed (in weeks from the onset of chemotherapy): FAMi, 29.6; FAMe, 34.4; FMe, 22.9; FIMe, 17.4. Two nontreatment variables were found to be significantly associated with survival when analyzed using the Cox covariate model: pretreatment performance status (P less than 0.0001), and presence or absence of measurable metastatic disease (P less than 0.001). After adjustment for the effects of these and other clinical variables, two treatment regimens were found to be associated with improved survival: FAMi therapy (P less than 0.01), and FAMe therapy (P = 0.07). Toxicity was, in general, moderate and consisted primarily of gastrointestinal side effects and myelosuppression. We conclude that the FAMi and FAMe regimens are superior to the FIMe and FMe regimens in the management of advanced gastric cancer.
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PMID:A comparative clinical assessment of combination chemotherapy in the management of advanced gastric carcinoma: The Gastrointestinal Tumor study Group. 703 63

A liposome-entrapped liposome form of Adriamycin (Lip-ADM) has been demonstrated to cause less myocardial and gastrointestinal toxicity than free ADM. In the present study, Lip-ADM prepared by the remote loading method was administered to 3 patients with metastatic adenocarcinoma of the liver via a reservoir with the catheter located in the proper hepatic artery. The primary tumor was gastric cancer in 2 patients and sigmoid colon cancer in 1. Lip-ADM was administered at doses of 10, 20 or 50 mg per time. The total ADM dose was 170, 490, and 760 mg, respectively. No severe adverse effects, such as nausea, vomiting, stomatitis, alopecia or cardiotoxicity, were observed in any of the patients. Although mild leukocytopenia (2,800/microliters) was observed in 1 patient, anemia or thrombocytopenia did not occur. The survival time was respectively 6, 15, and 17 months from the start of Lip-ADM administration. A partial response was obtained in 1 patient and stable disease in 1 patient. Administration of Lip-ADM via a reservoir appears to be a useful treatment for patients with metastatic adenocarcinoma of the liver, since the low toxicity of this preparation allows an increase of the total dose of ADM.
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PMID:Intra-arterial liposomal adriamycin for metastatic adenocarcinoma of the liver. 758 1

Controlled randomized studies that compared surgery alone to adjuvant chemotherapy for gastric cancer were reviewed. The amount of residual tumor after surgery, selection of drug regimens, compliance with drug administration, and trial design seem to be responsible for the success of adjuvant chemotherapy. Though there are few beneficial regimens of adjuvant chemotherapy with statistical significance, single drug therapy with mitomycin C (MMC) and combination therapy with 5-fluorouracil (5FU) and methyl-CCNU, MMC/5FU/cytosine arabinoside (MFC), and 5FU/Adriamycin/MMC (FAM) seem to have potential survival benefit for patients with curative surgery. Incorporation of new drugs into adjuvant or neoadjuvant chemotherapy might open a new aspect of multimodality therapy for gastric cancer.
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PMID:Review of adjuvant chemotherapy for gastric cancer. 767 2

Adenocarcinoma of the stomach represents a significant problem worldwide. The only known curative treatment of gastric cancer is complete surgical resection of the stomach tumor with surrounding lymph node-bearing areas. However, as many as 50% to 90% of patients undergoing gastric tumor resection relapse and die of cancer. Adjuvant chemotherapy has been used to prevent recurrence of gastric cancer after surgical resection. Single agents including thiotepa and fluorodeoxyuridine have no benefit as adjuvant therapy. Likewise, combination chemotherapy including 5-fluorouracil (5-FU) plus methyl-CCNU, 5-FU plus Adriamycin plus mitomycin C (FAM), and mitomycin C plus 5-FU plus cytosine arabinoside do not result in overall improved survival. Combined modality irradiation plus fluorinated pyrimidine, however, has resulted in long-term survival of patients with known residual gastric cancer. The newest clinical trial in postoperative gastric cancer being performed in the United States will test 5-FU plus leucovorin plus irradiation in a prospectively randomized study in patients with resected stage IB through stage IV stomach cancer. This surgical study, designed with excellent prospective quality control, is actively accruing patients and will be completed in 1.5 to 2.0 years.
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PMID:Adjuvant treatment of gastric cancer. 775 27

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

A phase II trial of etoposide (100 mg/m2) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m2) on days 1, 7, and cisplatin (30 mg/m2) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients, 2 (10%) had a complete response (CR), 7 (33%) had a partial response (PR), 4 (20%) showed no change and 8 progressed (38%). The mean duration of response (CR+PR) was 8.4+ months. Survival of the whole group was 7.5+ months. Treatment was quite well tolerated by most patients on an outpatient basis. Grade 3 vomiting and leukopenia were seen in 30% and 35% of cases respectively. One patient had grade 3 esophagitis, and 1 patient was hospitalized for severe grade 4 febrile leukopenia. Although the EAP regimen cannot be considered a standard therapy for gastric cancer, the EAP schedule employed in this study seems to be better tolerated than those reported by other authors, and can safely be given on an outpatient basis.
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PMID:Etoposide, doxorubicin (Adriamycin) and cisplatin regimen in advanced gastric adenocarcinoma: experience with a lower dose schedule. 804 20

Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor alpha (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.
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PMID:Tumour-cell-induced production of tumour necrosis factor by monocytes of gastric cancer patients receiving BCG immunotherapy. 842 10


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