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

Capecitabine (Xeloda, Roche, Monza), a fluoropyrimidine carbamate, is an orally administered drug that delivers fluorouracil (5-FU) selectively to the tumor. The drug has demonstrated activity in metastatic breast cancer, pancreatic cancer and colorectal cancer. In this case report the authors describe an unusually and reversible cardiac side effect which occurs to 39-year-old patient treated with capecitabine 2000 mg/m2/day for advanced gastric cancer. It is important to note that the safety data from clinical trials indicate that capecitabine has a toxicity profile typical of infused fluoropyrimidines. However, none of the studies described cardiac side effects.
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PMID:Acute cardiotoxicity during capecitabine treatment: a case report. 1150 78

Capecitabine and docetaxel have considerable single-agent activity in gastric cancer with distinct mechanisms of action and no overlap of key toxicities. A synergistic interaction between these two drugs is mediated by taxane-induced upregulation of thymidine phosphorylase. We investigated the activity and the feasibility of capecitabine and docetaxel combination chemotherapy in patients with previously untreated advanced gastric cancer (AGC). From September 2001 to March 2003, 42 patients with AGC received 21-day cycles of oral capecitabine (1250 mg x m(-2) twice daily on days 1-14) and docetaxel (75 mg x m(-2) i.v. on day 1). The patients received a total of 164 cycles of chemotherapy. The median age was 53.5 years (range 33-73 years). The overall response rate in the 38 efficacy-evaluable patients was 60% (95% confidence interval, 45-74%). The median progression-free survival was 5.2 months (range, 1.0-15.5+ months) and the median overall survival was 10.5 months (range, 2.9-23.7+ months). The most common grade 3/4 adverse events were hand-foot syndrome (HFS: G3 50%), neutropenia (15%) and leucopenia (12%). Further studies of this combination are clearly warranted, albeit with lower doses of both agents (1000 mg x m(-2) twice daily and 60 mg x m(-2)) to reduce the rate of HFS and onycholysis.
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PMID:A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. 1505 50

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.
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PMID:Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy. 1565 40

Gastric cancer is the second most frequent cancer in the world. Approximately 84% of patients with gastric cancer will have advanced disease and median survival of these patients without chemotherapy is only 3-4 months. "Classical" chemotherapy regimens, mainly CF (cisplatin plus infusional 5FU) and ECF (cisplatin plus infusional 5FU plus Epirubicin) obtain responses in 20-40% of the patients and improve quality of life. Nevertheless, duration of these responses is short with very few complete responses. Median time to tumor progression (TTP) with these regimens is only about 4-5 months and median survival does not exceed 7-10 months. Moreover, benefit seems to be limited to patients with good performance status and treatment toxicity and discomfort are not negligible, specially that of regimens with cisplatin or infusional 5FU. Trying to improve these results, the incorporation of new drugs has been explored. Among the new combinations, the more developed ones are those with Docetaxel (DCF), oxaliplatin (EOX, FLO), Capecitabine (EOX, cisplatin-Xeloda) and irinotecan (ILF). We have final results from Phase III trials that suggest that all these regimens could have a role in the treatment of these patients but survival is still very poor and toxicity remains important. It would be interesting to investigate other new combinations and the incorporation of drugs directed against new therapeutic targets in this setting. It would be of utmost interest that these clinical trials would also explore clinical and molecular prognostic and predictive factors.
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PMID:Chemotherapy of advanced gastric cancer. 1737 98

Since the routine introduction of chemotherapy for advanced gastric cancer in the early 1990 s, median survival for gastric cancer has improved from 3 months, with best supportive care alone, to > 11 months in recently reported Phase III trials of triplet chemotherapy. Capecitabine is an orally-active fluoropyrimidine, which is selectively metabolised to fluorouracil in tumour cells. The combinations of platinum compounds and capecitabine have been evaluated in two recent, large, Phase III trials demonstrating non-inferiority in efficacy compared with platinum plus continuous infusion fluorouracil. In view of the convenience and flexibility of patients in adjusting dosage when encountering toxicities, capecitabine is replacing continuous infusion fluorouracil as the backbone of combination chemotherapy in advanced gastric cancer patients. Future trials evaluating biologicals are now incorporating capecitabine combinations as control arms in both advanced disease and peri-operative settings in gastric cancer.
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PMID:Capecitabine in advanced gastric cancer. 1795 4

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy. The median age was 81 years (range 76-85). The median duration of treatment was 113 days (range 24-238 days). No grade 4 toxicity was observed. One patient had grade 3 nausea and vomiting, and one had grade 3 diarrhea. Partial responses were observed in six patients with colorectal cancer, and in one patient with gastric cancer. This study suggests that continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated, and that it allows for the simplification and ease of dosing in elderly patients with metastatic colorectal and gastric cancer.
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PMID:Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the Multidisciplinary Oncology Group on Gastrointestinal Tumors. 1804 34

Although the role of systemic chemotherapy has been established for the treatment of advanced gastric cancer, the prognosis of these patients remains poor, with a median overall survival of less than 1 year. Based on the results of several randomized Phase III trials, 5-fluorouracil continuous infusion plus cisplatin, with or without epirubicin, has become the global reference regimen for this patient population. However, treatment with fluorouracil infusion requires either frequent hospitalizations or the use of a central venous access device, harboring potential complications. Capecitabine, a tumor-activating oral prodrug of fluorouracil, may be more advantageous in terms of patient convenience, safety and efficacy. Two recent randomized Phase III trials have shown that capecitabine could replace infusional fluorouracil in cisplatin-based regimens. Furthermore, Phase II trials have shown that many other capecitabine-based doublet or triplet chemotherapy regimens incorporating newer cytotoxic agents are active and well tolerated. Many promising biological agents are now being tested in Phase III trials, incorporating capecitabine combinations as control arms, in patients with advanced gastric cancer.
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PMID:Capecitabine in the treatment of advanced gastric cancer. 1840 32

Capecitabine, an oral fluoropyrimidine and 5-fluorouracil (FU) prodrug recently approved for the treatment of metastatic colon and breast cancer, is currently under investigation in patients with gastric cancer. It has the advantage of oral administration, and good tolerability with its activity being comparable with intravenous 5-FU. Lupus erythematosus and lupuslike drug eruptions have been observed after 5-FU treatment, but so far no cases of subacute cutaneous lupus erythematosus have been described in patients treated either with capecitabine or 5-FU. We report a patient who developed subacute cutaneous lupus erythematosus after administration of 5-FU and capecitabine.
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PMID:Occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine. 1862 80

The efficacy of chemotherapy for advanced gastric cancer with palliative intent compared with supportive care alone is now widely accepted. However, the survival advantage is small, and no internationally accepted standard regimen has emerged. This study is performed to evaluate the response rate, time to progression, and safety of the combination of capecitabine (1000 mg/m twice daily, days 1-14) plus oxaliplatin (130 mg/m as a 2-h intravenous infusion on day 1) every 3 weeks, in previously untreated Chinese patients with advanced gastric cancer. Sixty-five (95.6%) of the 68 patients were assessable for response. Three cases of complete response and 34 cases of partial response were confirmed, giving an overall response rate of 54.4% [95% confidence interval (CI), 42.6-66.2%]. The median time to progression and overall survival for all patients were 5.7 months (95% CI, 2.0-8.8 months) and 10.5 months (95% CI, 5.0-15.1 months). The most severe hematologic adverse event was neutropenia, which occurred with grade 3 intensity in three (4.6%) patients and grade 4 in one (1.5%) patient. Thrombocytopenia and leukopenia occurred with grade 3 intensity in five (7.7%) and three (4.6%) patients, respectively. However, no grade 4 thrombocytopenia and leukopenia were observed. Grade 1/2 nausea/vomiting and diarrhea were observed in 33 (50.8%), 17 (26.2%), 26 (40%), 44 (67.7%), and 13 (20%) patients, respectively, and grade 3 nausea/vomiting and diarrhea were observed in one (1.5%) and four (6.2%) patients. Yet, no grade 4 nonhematologic toxicity was observed. Capecitabine/oxaliplatin combination chemotherapy is active in Chinese patients with previously untreated advanced gastric cancer.
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PMID:Multicenter phase II study of capecitabine plus oxaliplatin as a first-line therapy in Chinese patients with advanced gastric cancer. 1869 95

Double and triplet regimens comprising a fluoropyrimidine and a platinum compound, with or without an anthracycline or taxane are accepted standards of care for advanced gastric cancer. Capecitabine, an oral fluoropyrimidine designed to selectively deliver 5-fluorouracil (5-FU) to tumor cells, is safe and effective in combination chemotherapy regimens for advanced gastric cancer, and it is noninferior to 5-FU for survival. As capecitabine is more convenient to administer than infused 5-FU, avoiding the need for central venous access and the associated risk of complications, it is also an accepted alternative to 5-FU within perioperative combination chemotherapy regimens for resectable gastric cancer.
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PMID:Capecitabine in gastric cancer. 1884 73


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