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)

There exist no common recommendations for palliative therapy of gastrointestinal cancer. Fluorouracil has been used for a long time, remission rates reported range from 0% to 80%. In larger series they figure about 20% but without prolongation of survival in responders. Although this drug is used for 20 years optimal dose and timing is still unknown. By combination of fluorouracil with other drugs remission rates were improved and in responders survival was prolonged (mitomycin C and/or adriamycin in gastric cancer, methyl-CCNU in colorectal cancer). The results of adjuvant chemotherapy of gastrointestinal cancer are contradictory, the routine usage is not recommendable. Adjuvant as well as palliative chemotherapy must be improved by controlled clinical trials.
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PMID:[Chemotherapy of gastrointestinal tumors (review of the literature)]. 8 61

In this study, 139 eligible and evaluable patients with advanced gastric cancer, measurable disease, and no prior chemotherapy were randomized between treatment with Adriamycin alone, 5-fluorouracil (5-FU) plus mitomycin C, and 5-FU plus methyl-CCNU. Objective responses were seen in eight of 37 patients (22%) receiving Adriamycin, in 17 of 53 (32%) receiving 5-FU plus mitomycin C, and in 12 of 49 (24%) receiving 5-FU plus methyl-CCNU. Median durations of response were 4, 3 1/2, and 8 1/2 months, respectively. Sixty-one patients were treated after previous failure to other chemotherapy regimens. Response rates were seen in seven of 47 patients (15%) receiving Adriamycin, in two of nine receiving 5-FU plus mitomycin C, and in one of five receiving 5-FU plus methyl-CCNU. Complete responses were observed more frequently with Adriamycin and with 5-FU plus methyl-CCNU than with 5-FU plus mitomycin C. Although 5-FU plus methyl-CCNU had a slight advantage in interval to disease progression, this was not statistically significant. Median survival for all previously untreated patients was slightly greater than 17 weeks, and there was no meaningful or significant survival difference between the three treatment groups.
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PMID:Phase II-III chemotherapy studies in advanced gastric cancer. Eastern Cooperative Oncology Group. 39 81

In this multi-institutional study of advanced gastric cancer, 141 eligible and evaluable patients were treated with either (a) Adriamycin alone, (b) a combination of 5-fluorouracil, Adriamycin, and methyl-CCNU (FAMe), or (c) a combination of 5-fluorouracil, mitomycin C, and cytosine arabinoside (FMC). In patients with measurable disease and no prior chemotherapy, objective responses were seen in four of 17 patients (24%) receiving Adriamycin alone, in seven of 15 (47%) receiving FAMe, and in three of 18 (17%) receiving FMC. In previously treated patients with measurable disease, objective responses were seen in three of 17 patients (18%) receiving Adriamycin alone and in one of 11 (9%) receiving FMC. In previously untreated patients with both measurable and nonmeasurable disease, FAMe showed a significant advantage over both Adriamycin alone and FMC with regard to interval to disease progression and survival. In comparing Adriamycin alone with FMC in previously treated patients, intervals to disease progression and survival were essentially identical.
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PMID:Phase II-III chemotherapy studies in advanced gastric cancer. The Gastrointestinal Tumor Study Group. 39 82

Patients with a wide range of gastrointestinal cancers have been treated with nitrosoureas by the Eastern Cooperative Oncology Group. Methyl-CCNU, CCNU, and streptozotocin have been evaluated as single agents in the treatment of colorectal carcinoma. Methyl-CCNU has had an extensive trial in gastric carcinoma as a single agent and in combination with 5-fluorouracil (5-FU). It has also been used to treat pancreatic carcinoma and, in a few patients, carcinoma of the biliary tract. In gastric cancer it would appear that a synergistic effect on response rates has resulted from the combination of methyl-CCNU and 5-FU. The addition of cyclophosphamide to this combination as an induction agent detracted significantly.
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PMID:Nitrosoureas: useful agents for the treatment of advanced gastrointestinal cancer. 78 99

One hundred and forty-six previously untreated patients with advanced gastric cancer were assigned at random to therapy with the following regimens: 1) Methyl CCNU alone; 2) Methyl CCNU with cyclophosphamide induction; 3) 5-fluorouracil (5-FU) + methyl CCNU; and 4) 5-FU + methyl CCNU with cyclophosphamide induction. Cyclophosphamide induction produced an objective response rate of only 8%. In addition, it added to hematologic toxicity and detracted from the therapeutic activity of subsequent treatment. Methyl CCNU was relatively ineffective therapy with an overall objective response rate of 8%. The response rate to 5-FU + methyl CCNU without cyclophosphamide induction was 40% and this was significantly superior to all other regimens. The survival time of all patients treated with 5-FU + methyl CCNU was significantly superior to that of all patients treated with methyl CCNU alone.
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PMID:Sequential and combination chemotherapy of advanced gastric cancer. 78 91

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with alpha-difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.
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PMID:Schedule dependent potentiation of antitumor drug effects by alpha-difluoromethylornithine in human gastric carcinoma cells in vitro. 169 47

In previous Gastrointestinal Tumor Study Group (GITSG) reports, gastric cancer patients with locally unresectable disease, treated with combined radiation and chemotherapy had a shorter median survival (40 weeks) but more remained alive at 4 years (18%) when compared to those randomized to receive chemotherapy alone (76 weeks and 6%, respectively). To further test the concept that combined modality therapy might increase the number of long-term survivors, a second protocol was designed, but with three major modifications. A course of chemotherapy would precede the 5-fluorouracil-potentiated radiation therapy. Doxorubicin would be added to the 5-fluorouracil plus methyl-CCNU combination. Radiation therapy would be given as a single course of 4320 cGy, with 5-fluorouracil given daily for 3 days at the beginning and end of the course. Median survival of 46 patients treated with chemotherapy alone was 59 weeks, with 11% alive after 3 years. Following combined modality therapy, median survival was 62 weeks, but only 7% lived 3 years. Although the problem of early deaths in the combined modality group was resolved, long-term survival with combination therapy was not demonstrated in this study.
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PMID:The concept of locally advanced gastric cancer. Effect of treatment on outcome. The Gastrointestinal Tumor Study Group. 170 Sep 27

Adjuvant treatment is based on the concept that surgery is only potentially curative and that apparently localized disease has extended beyond surgical resection or is already disseminated. Although death might be related to local recurrence as well as to disease dissemination, most of the trials have tested only one adjuvant modality. Among many negative and non-contributory studies, very few positive results were obtained: in rectal cancer it seems that pre-operative and perhaps postoperative radiotherapy may reduce the incidence of local recurrences, and in colon cancer patients treated with Methyl-CCNU, vincristine and 5-fluorouracil (5-FU) had a significant increase in survival. In colon cancer, the lack of active drug might at least partly explain negative studies, but in gastric cancer the most active combination in advanced disease has failed to demonstrate an improvement of survival in the adjuvant setting. Future trials should take account of this succession of negative trials.
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PMID:The future of adjuvant treatment in gastrointestinal cancer. 218 51

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.
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PMID:An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer. 330 95

After en bloc resection of gastric adenocarcinoma, 180 patients were randomized to 2 years of 5-fluorouracil (5-FU) + semustine (MeCCNU) chemotherapy or to observation only. After a median follow-up time of 64 months, 48 of 89 control patients and 51/91 treated patients recurred (P less than 0.71). The sites of recurrent cancer were similar for both groups: liver, 32%; local esophagus or stomach, 51%; abdominal nodes and peritoneum, 38%; and extra-abdominal nodes, 14%. The survival curves overlap; 51/89 controls and 57/91 treated patients died with a median survival of 32.7 and 36.6 months, respectively (P less than 0.73). Treated patients experienced clinically important hematologic toxicity and two treated patients died of marrow failure with leukemia. Because of the toxicity and the lack of effectiveness, adjuvant 5-FU + MeCCNU is not recommended for patients with resectable gastric cancer.
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PMID:Postoperative adjuvant 5-fluorouracil plus methyl-CCNU therapy for gastric cancer patients. Eastern Cooperative Oncology Group study (EST 3275). 388 31


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