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)

The recent successes being achieved with combination chemotherapy regimens, such as FAMTX (fluorouracil [5-FU], doxorubicin, methotrexate), EAP (etoposide, doxorubicin, cisplatin), and ELF (etoposide, leucovorin, 5-FU), strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remissions (CRs). Moreover, some of these CRs were histopathologically confirmed. The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. Thirty-six patients with LAD had been treated in a phase II trial with preoperative EAP, inducing 24 (70%) overall remissions (two clinical CRs, six pathologic CRs, 16 partial remissions [PRs] in 35 evaluable patients. Twenty-one patients were disease-free after chemotherapy with or without second-look surgery. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease-free. The expected survival of patients with unresectable LAD is approximately 4 to 6 months without any treatment and 6 to 9 months with standard chemotherapy. Compared with the latter results, the preoperative use of effective regimens (eg, EAP) seems to improve prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stages IIIa or IIIb). However, partly because of the severe toxicities (myelosuppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens for the following reasons: Two of three patients with gastrointestinal disease are older than 60 years. Nontumorous diseases of the cardiovascular system, kidney, and others are frequent in this age group and may complicate or even prevent treatment with aggressive regimens. Considering the predominantly palliative treatment intentions in far advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination ELF in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53% (27 of 51) including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. Only 16% and 4% of patients, respectively, experienced WHO grades 3 and 4 leukopenia. Nausea/vomiting and mucositis/stomatitis were mild.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in the treatment of gastric carcinoma. 230 69

Thirty one patients with diagnosis of Gastric Cancer were admitted in this study. Median age was 71 years (range 24-82). Twenty two were male. No one had previous chemotherapy. Functional capacity was 0-1 in 26/31 (60.6%). More common symptoms were: loss of weight 21/31 (75.1%) and abdominal pain in 13/31 (40.3%). Ten patients were Borrmann III and nine Borrmann IV. Twenty one had surgery: 12 palliative gastrectomy and 9 exploratory laparatomy. Twenty three cases were adenocarcinoma and 8 undifferentiated carcinoma. FEM regimen was administered (5 Fluoruracil 600 mg/m2/day 1 and 8, Epidoxorubicin 30 mg/m2/day 1 and Mitomycin 10 mg/m2/day 1). Ten of 24 patients (41.7%) achieved partial remission with a median survival of 10.5 months. Three patients achieved subjective response with a median survival of 6 months. Median survival for the non response was 3 months (range 2-7 months). Survival difference between responders and no responders was statistically significant. Survival among the adjuvent group was 5.7 months (range 2-16 months). One out of three patients survived without evidence of disease at the end of this study. Twenty three patients died and 5 were lost to follow up. Alopecia was the most common secondary effect in 74%, nausea and vomiting in 60% and leukopenia below 3000 x mm3 in 54%. Cardiotoxicity was not documented in any case.
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PMID:[Combined chemotherapy with the FEM protocol in advanced gastric cancer]. 251 38

Fourteen patients with advanced gastric cancer consisting of seven primary cases and seven recurrent cases were treated with the combination of etoposide, adriamycin and cisplatin (EAP). One of the primary cases (14%) and three of the recurrent cases (43%) responded to the therapy, but a high incidence of toxicities including leukopenia, thrombocytopenia, alopecia, nausea and vomiting was observed. It is concluded that EAP therapy can be useful in the treatment of advanced gastric cancer if countermeasures to the toxicities of these drugs are considered.
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PMID:[Combination therapy with etoposide, adriamycin and cisplatin in advanced primary and recurrent gastric cancer]. 259 54

The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamycin and methotrexate were given as i.v. infusions on day 1; 24 h following methotrexate administration, patients received an i.v. infusion of 5-fluorouracil concomitantly with oral leukovorin factor (given over 48 h). Methotrexate levels were monitored regularly in all patients, and courses were repeated every 3 weeks. The median dose levels per course were 50 mg/m2 (range, 40-60 mg/m2) for Adriamycin, 1,000 mg/m2 (range, 650-1,250 mg/m2) for 5-fluorouracil, and 500 mg/m2 (range, 160-625 mg/m2) for methotrexate. Of 36 evaluable patients, 8 (22%) achieved an objective response, including 1 complete remission. Stable disease was noted in 11 patients and a minor tumor regression occurred in 1. The median survival duration of all patients was 6 months (range, 2-31+ months). AMF was well tolerated; toxicities were mild to moderate, most frequently involving nausea and vomiting, mucositis, and neutropenia with or without fever. There was no death directly attributable to chemotherapy. Although the AMF regimen used a well-documented preclinical concept of synergism between methotrexate and 5-fluorouracil, response and survival results suggest a modest activity of this combination in patients with gastric cancer. Better preclinical models are necessary for the development of effective combination chemotherapy.
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PMID:Phase II study of adriamycin with sequential methotrexate and 5-fluorouracil (AMF) in gastric carcinoma. 272 Aug 90

A total of 23 patients with advanced malignancies received escalating doses of epirubicin (100-120 mg/m2) i.v. at 3-week intervals; 15 had received previous chemotherapy. In all, 46 courses of chemotherapy were given. Mucositis (grade II or III) occurred in 47% of courses at 120 mg/m2, but in only 15% of courses at 115 mg/m2. Myelotoxicity was manifest as leucopenia, with a median white blood count nadir of 1.9 (range, 0.8-7.0) x 10(9)/l. Nausea and vomiting were generally well controlled by prophylactic antiemetic therapy. Alopecia was WHO grade 0 in 2 patients, grade I in 1, grade II in 5 and grade III in 14. No renal or hepatic toxicity was noted, and there were no episodes of congestive cardiac failure. One fatal coronary thrombosis (proven at post-mortem examination) occurred 48 h after a dose of 115 mg/m2. Four patients developed thrombophlebitis at the injection site that was not dose-related; it occurred at doses between 100 and 120 mg/m2. Two patients who had been given chemotherapy in the past had complete responses (one penile carcinoma, one gastric carcinoma). Six patients had partial responses, including two with breast cancer, one with gastric cancer and three with sarcoma. Intermediate-dose epirubicin was well tolerated up to 120 mg/m2, when mucositis became a significant clinical problem. Preliminary data suggest promising activity in gastric cancer, breast cancer and a variety of sarcomas.
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PMID:Experience with intermediate-dose (110-120 mg/m2) epirubicin. 272 Aug 92

Twenty patients with focal malignant obstruction of the major bile ducts (6 cholangiocarcinoma, 8 colorectal, 3 hepatoma, 2 unknown primary, and 1 gastric cancer) were treated on a protocol examining the toxicity and efficacy in relieving jaundice of external beam radiation therapy (4500 cGy in 300 cGy fractions) combined with continuous hepatic arterial (15 patients) or peripheral venous (5 patients) fluorouracil infusion. Toxicity of this regimen consisted of anorexia with mild nausea and vomiting in 55% of patients and gastric ulceration (responsive to medical management) in 15% of patients. One patient exhibited transient grade 2 hepatic toxicity and one had asymptomatic grade 4 leukopenia. Of 14 patients treated without prior biliary drainage, 8 exhibited a decrease in bilirubin levels from a mean of 14.5 mg/dl to 1.5 mg/dl. Four of six patients with biliary drainage catheters at the start of treatment were able to have them removed without reobstruction. For the 8 responding patients among those who did not have cholangiocarcinomas, the median response duration was 5 months with a median survival from treatment of 6.5 months. For the 4 responding patients with cholangiocarcinoma, the median response duration was 16 months with a median survival from treatment of 20 months. All responders did not have a return of jaundice due to reobstruction of the major ducts (until death or to the present). All responders who have died did so due to tumor progression outside of the treated field except for one who died of unrelated causes. The mean number of proven or presumed episodes of cholangitis per patient was virtually identical in those without (1.8) and those with stents/tubes (1.4, p = 0.561). This regionally focused combined modality cytotoxic therapy was able to relieve obstruction in the majority of patients without excess morbidity (including a lack of any detectable increase in sepsis). Thus, it appears feasible to consider randomized studies of this cytotoxic approach versus standard mechanical drainage procedures to define the relative risks and benefits of each.
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PMID:Combination chemo-radiation therapy for jaundice due to focal malignant obstruction of the major bile ducts. 277 30

Taxol, selected for clinical trial because of its animal antitumor activity and unique structure and mechanism of action, was administered in Cremophor by i.v. infusion over 6 h in a phase I study. Eastern Cooperative Oncology Group toxicity grading was used. Eighty-three taxol courses were administered to 34 patients. Grade 3-4 hypersensitivity reactions occurred in 4 of 13 courses at the first 2 dose levels, but premedication with dexamethasone, diphenhydramine, and cimetidine resulted in only 3 additional Grade 2 reactions in the next 70 courses. Neurotoxicity, which resolved or improved after stopping therapy, was Grade 1 with 2 of 10 courses of 230 mg/m2 and Grades 1-3 after 11 of 12 courses of 275 mg/m2. Leukopenia, first seen (Grade 1) after 1 of 8 75 mg/m2 courses, was Grades 3-4 after 10 of 34 courses of 175-230 mg/m2 and 10 of 12 courses of 275 mg/m2. The WBC nadir occurred at a median of 10 days and the median time required for normalization of the WBC was 18 days. Alopecia began 2-3 weeks posttaxol in 2 of 9 patients treated with 75-135 mg/m2 and in all 16 patients (Grade 3) treated with 175-275 mg/m2. Grades 1-2 nausea and vomiting occurred in about one-third of the patients treated at a dose of 105 mg/m2 or more. Taxol disappearance from plasma was biphasic; half-lives of the first and second phases after a 275 mg/m2 dose were 0.32 and 8.6 h, respectively. The apparent volume of distribution was 55 liters/m2, and the peak plasma concentration with a dose of 275 mg/m2, which occurred immediately postinfusion, was approximately 8 microM. Only 5% of parent drug was excreted in the urine within 24 h. Minor objective responses were noted in one patient with gastric cancer and another with ovarian carcinoma. In addition, one patient with massive ascites due to metastatic adenocarcinoma from an unknown primary had only minimal sonographic evidence of ascites for 6 months posttreatment. Neurotoxicity and leukopenia were dose limiting in this schedule. The recommended phase II trial dose is 250 mg/m2, with premedication.
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PMID:Phase I clinical and pharmacokinetic study of taxol. 288 37

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.
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PMID:Phase II clinical evaluation of doxifluridine. 294 45

Monozygotic twins developed gastric cancers that were found almost simultaneously. A 47-year-old man complained of nausea and vomiting; an upper gastrointestinal series and endoscopy revealed advanced gastric cancer invading the serosa. Palliative subtotal gastrectomy was performed. In his asymptomatic twin a gastric polyp was detected during a screening examination, and this was observed for 2 years. After the former twin had undergone surgery, the latter twin was given a detailed endoscopic examination, and biopsy revealed gastric cancer limited to within the mucosa. Curative subtotal gastrectomy was performed. The noncancerous gastric mucosa of the former twin showed severe intestinal metaplasia, but that in the latter showed only spotty metaplasia. They had lived together for 40 years, but the former was a heavy smoker and drank alcohol, while the latter did not. These differences in taste might have contributed to the observed difference in intestinal metaplasia, which indicates chronic mucosal damage.
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PMID:Simultaneous gastric cancer in monozygotic twins. 305 90

Seventeen patients with advanced gastrointestinal cancer were treated with a combined chemotherapy of UFT with Adriamycin (UFT-A). The UFT-A regimen consisted of UFT, 600 mg/body daily. As for the Adriamycin, 10 mg/body was give intravenously from day 1-4 and was repeated every two weeks. Partial responses were seen in 7 cases (41%) (5 cases of gastric cancer, 1 case of colon cancer, and 1 case of bile-duct cancer) out of 17 evaluable patients (7 cases of gastric cancer, 3 cases of colon cancer, 4 cases of biliary tract cancer, and 3 cases of pancreatic cancer). Two patients had minor responses, and in eight patients their disease had stabilized. As for side effects, nausea and vomiting occurred in seven patients (41%), and anorexia was observed in eight patients (47%). Two patients (12%) showed a leukopenia count of less than 2,000/mm3 and none of these seventeen patients had thrombocytopenia, of less than 5 x 10(4)/mm3. Considering these results, UFT-A therapy appears to be useful in cases of advanced gastrointestinal cancer, especially gastric cancer.
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PMID:[Combination chemotherapy of UFT with adriamycin in advanced gastrointestinal cancer]. 311 75


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