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)

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

In vitro antitumour effects of docetaxel (Taxotere) were examined in nine cultured human gastric cancer cell lines and 18 clinical gastric cancer specimens. In vivo antitumour effects were examined in human gastric cancer xenografts in nude mice. The activity was compared with paclitaxel (Taxol). Docetaxel was more effective than paclitaxel in six of the nine cell lines and the effectiveness rates of docetaxel and paclitaxel were 56% (10/18) and 6% (1/17), respectively, in the clinical gastric cancer specimens. In vivo docetaxel showed superior antitumour effect on well differentiated (MKN-28), poorly differentiated (MKN-45) and undifferentiated (KKLS) gastric cancer xenografts. We conclude that docetaxel promises to be clinically active against gastric carcinomas.
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PMID:Evaluation of antitumour effects of docetaxel (Taxotere) on human gastric cancers in vitro and in vivo. 866 32

We initiated a phase II study to determine the efficacy of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with advanced esophageal or gastric cancer. Objective tumor responses, duration of response, time to disease progression, overall survival, and toxicity profile are the end points evaluated in this study. The study includes patients with locally advanced metastatic or recurrent esophageal or gastric cancer with no history of prior chemotherapy or radiation treatment. Patients are required to have a performance status of 0 to 2 and no organ failure. Staging diagnostics include computed tomography scans and endoscopic ultrasound when appropriate. Starting dose of paclitaxel is 200 mg/m2, and carboplatin is given to achieve an area under the concentration-time curve of 5.0. Dose escalation is attempted if nadir counts permit. Seventeen patients have registered so far. Of those, three are not evaluable for efficacy analysis: one has not been on study long enough to be assessed for response and the other two are not assessable for objective tumor response. Three patients with gastric cancer have achieved partial responses. Two of five patients with esophageal cancer responded (partial response) to this treatment. Dose escalation by one step was feasible in approximately half the patients. There were no episodes of neutropenic fever. Carboplatin and paclitaxel given on an outpatient basis is well tolerated and an interesting regimen for the treatment of patients with advanced gastric or esophageal cancer.
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PMID:A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. 942 74

The current phase II study evaluates the safety and efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and 5-fluorouracil (5-FU) plus folinic acid in patients with advanced gastric cancer. Paclitaxel 175 mg/m2 was given intravenously over 3 hours on days 1 and 22; folinic acid 500 mg/m2 given intravenously over 2 hours followed by 5-FU 2,000 mg/m2 given intravenously over 24 hours was administered on days 1, 8, 15, 22, 29, and 36. Six weeks of treatment were considered one cycle, and each cycle was followed by 2 weeks off treatment. Twenty-two patients (six women and 16 men) with advanced/metastatic gastric cancer were entered on trial. All patients are evaluable for response and toxicity. None had received prior chemotherapy. Radiologically metastatic sites included gastric lymph nodes (64%), liver (36%), lungs (18%), peritoneum (18%), bone (9%), and skin (5%). No complete responses were observed. Seven patients (32%; 95% confidence interval, 12% to 52%) had a partial response. Sites of partial responses included the lungs, skin, lymph nodes, and locally advanced tumor. Twelve patients (55%) had stable disease and three (14%) had disease progression. At a median follow-up of 12 months (range, 1 to 17+ months), the median overall survival for all patients was 11 months (range, 1 to 17+ months; 95% confidence interval, 6.8 to 18.2) and the median progression-free interval was 8 months (range, 1 to 13+ months; 95% confidence interval, 4.7 to 9.8). Severe nonhematologic toxicities were alopecia (45%), fever/infection (9%), diarrhea (5%), and nausea/vomiting (5%). Grade 3/4 neutropenia occurred in three patients (14%). In summary, paclitaxel given every 3 weeks in combination with once-weekly, 24-hour continuous infusions of 5-FU/folinic acid is active in advanced gastric cancer and appears to achieve response rates comparable to regimens like etoposide/folinic acid/5-FU or 5-FU/doxorubicin/methotrexate. The toxicity of this new combination is moderate and allows treatment in an outpatient setting. Ongoing studies are evaluating the activity of paclitaxel combined with weekly continuous infusions of 5-FU/folinic acid with or without cisplatin.
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PMID:Paclitaxel and weekly 24-hour infusion of 5-fluorouracil/folinic acid in advanced gastric cancer. 942 77

An effective locoregional therapy is needed for adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may enhance the effect of radiation therapy (RT). Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent RT (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer. This finding suggested that paclitaxel/RT was a rational treatment approach for other malignancies that frequently harbor p53 mutations, such as upper gastrointestinal malignancies. We completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancer. The maximum tolerated dose of paclitaxel was 50 mg/m2/wk for 6 weeks with abdominal RT. The dose-limiting toxicities were abdominal pain within the radiation field, nausea, and anorexia. Phase II studies are now under way. Twenty-five patients with locally advanced pancreatic cancer have been entered at the phase II dose level of paclitaxel 50 mg/m2/wk with concurrent RT (total dose, 50 Gy). Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions (n = 2), asymptomatic grade 4 neutropenia (n = 3), and nonneutropenic biliary sepsis (n = 1). Of the first 18 assessable patients with pancreatic cancer treated on the phase II study, six obtained a partial response, for a preliminary response rate of 33%. In the phase II study for locally advanced gastric cancer, 20 patients have been enrolled. Of the first 19 patients who have completed treatment, nine (47%) had grade 3/4 toxicities, including nausea, anorexia, esophagitis, and gastritis. Of the first 16 patients with gastric cancer, complete and partial responses have been observed in one and eight patients, respectively, for a preliminary response rate of 56%. We have also completed treatment on 24 patients with potentially resectable adenocarcinomas of the gastroesophageal junction with neoadjuvant paclitaxel 60 mg/m2 and cisplatin 25 mg/m2, weekly for 4 weeks, with concurrent RT (total dose, 40 Gy) followed by surgical resection. Ten patients (41%) had grade 3/4 toxicities, including neutropenia, nausea, and dehydration. Of 24 patients, four complete responses (17%) and 14 partial responses (58%) were observed, for an overall response rate of 75%. Severe esophagitis was uncommon, making this a well-tolerated outpatient regimen for adenocarcinomas of the distal esophagus. These findings demonstrate that paclitaxel-based chemoradiation for locally advanced upper gastrointestinal malignancies is well-tolerated with substantial activity.
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PMID:Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. 1021 May 40

Vinorelbine (VNR) is a new vinca alkaloid derivative semi-synthesized by Potier et al. The antitumor activity of VNR was superior to other vinca alkaloid antitumor agents, and the neuro-toxicity of VNR was weaker than those of other vinca alkaloids. In nude mice xenografted human tumor models, VNR showed antitumor activity against eight of eleven tumor models (non-small cell lung cancer: 4/4, breast cancer: 2/3, colon cancer: 0/2, stomach cancer: 2/2). Especially, VNR showed tumor-regressive activity against LC-6 non-small cell lung cancer and MX-1 breast cancer. The antitumor activity of VNR against non-small cell lung cancer was superior to that of vindesine (VDS), which had been one of the key drugs of non-small cell lung cancer in the clinic. In combination chemotherapy, VNR plus cisplatin (CDDP) was better than VDS plus CDDP, which had been one of the standard regimens of non-small cell lung cancer chemotherapy. The potent antitumor effect of VNR with minor neurotoxicity was explained by VNR having stronger activity on mitotic microtubules than axonal microtubules. It was supposed that less activity of VNR against mitotic microtubules would be related to different composition of microtubule-associated TAU isoforms in the two types of microtubules. In non-small cell lung cancer, VNR resulted in a significantly higher response rate than VDS. In combination with CDDP, VNR resulted in longer survival than VDS with a significant log-rank test. In advanced breast cancer, VNR resulted in a high response rate in 1st line and 2nd line treatment. VNR is effective in combination with chemotherapeutic agents such as anthracycline, fluorouracil and Taxol. In Japan, the clinical trial in breast cancer is now ongoing.
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PMID:[Properties of antitumor activity of vinorelbine tartrate, a new vinca alkaloid antitumor agent]. 1108 18

BACKGROUND: Because chemosensitivity tests usually require a large amount of tissue, they are not used routinely in patients with unresectable gastric cancer. The aim of this study was to investigate whether apoptosis can be used as a sensitivity assay for chemosensitivity in small gastric cancer specimens.METHODS: Apoptosis, detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL), was investigated in small specimens of the MKN-1, MKN-45, and TMK-1 human gastric cancer cell lines as a marker of chemosensitivity following exposure to antineoplastic agents.RESULTS: Doxorubicin (DXR), SN-38 (active metabolite of irinotecan), and paclitaxel (Taxol) induced DNA fragmentation in MKN-45 and TMK-1 cells, but not in MKN-1. In contrast, neither 5-fluorouracil (5-FU) nor cisplatin (CDDP) induced DNA fragmentation in any of the three cell lines. Small pieces cut from tumors implanted in nude mice were exposed to the antineoplastic agents in culture medium for 24 h, and the percentage of TUNEL-positive cancer cells (TUNEL positivity) was examined. TUNEL positivity in all three cancers increased after exposure to DXR, SN-38, and Taxol, but not after exposure to CDDP or 5-FU. MKN-45 showed the highest TUNEL positivity with SN-38 and Taxol, and TMK-1 TUNEL positivity was highest with DXR. MKN-45 and TMK-1 were the most sensitive to these three antineoplastic agents in vitro, while MKN-1, with the lowest TUNEL positivity, was the least sensitive to these three antineoplastic agents. TUNEL positivity after exposure to Taxol correlated with the antitumor effects of this compound in an animal model.CONCLUSION: These results suggest that, in small gastric cancer specimens where apoptosis is implicated, TUNEL positivity may be applicable to a chemosensitivity test.
Gastric Cancer 2000 Aug 04
PMID:A model chemosensitivity test examining apoptosis in small specimens of gastric cancer. 1198 8

We previously reported some cancer testis antigens, especially for MAGE genes, to be expressed in a relatively high population of gastro-intestinal and breast cancers. TRAG-3 (Taxol resistant associated gene-3) may be another cancer testis antigen; however, its expression has still not been fully studied. The TRAG-3 expression was evaluated in a total of 57 cancer cell lines and 322 cancer samples of gastrointestinal and breast cancers by RT-PCR. TRAG-3 was expressed in 23/57 (40%) of the cell lines: the highest expression was found in gastric cancer (6/9: 67%), followed by esophageal (13/28: 46%), colon (3/11: 27%) and liver (1/4: 25%) cancers. In clinical samples, the expression was the highest in esophageal cancer (32/58: 55%), followed by liver (13/50: 26%), bile duct (5/27: 19%), gastric (5/50: 10%), breast (5/50: 10%) and colon (2/87: 2.3%) cancers. The TRAG-3 expression significantly correlated with the expression of MAGE-3 in esophageal cancer (p<0.05). As the TRAG-3 gene is located on Xq28, which is the same locus as the MAGE gene family, we found a frequent synchronous expression pattern with TRAG-3 and MAGE-3 in esophageal cancer.
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PMID:Expression of the TRAG-3 gene in human esophageal cancer: the frequent synchronous expression of MAGE-3 gene. 1668 91

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.
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PMID:An open, multi-centre, phase II clinical trial to evaluate the efficacy and safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric cancer. 1680 24

We examined a 32-year-old Japanese man who was clinically diagnosed with gastric cancer, type 4, and histopathologically diagnosed with mucinous and poorly differentiated adenocarcinoma (mucinous > poorly) of the stomach. We successfully established and characterized a cell line (designated as IGSK-2) derived from the ascitic fluid of the patient with recurrent and cisplatin-resistant carcinoma. The IGSK-2 cells grew in multi-layered culture in culture dishes. The cells secreted 18 pg/mL somatostatin, 9.1 mIU/mL human chorionic gonadotrophin (hCG), 8000 U/mL carbohydrate antigen 19-9 and 410 ng/mL carcinoembryonic antigen over 4 days of culture. The population doubling time was approximately 83 h. The susceptibility test of anticancer drugs revealed that IGSK-2 cells were sensitive to Taxol, but were not sensitive to cisplatin, 5-fluorouracil and irinotecan. Immunohistochemical staining revealed that the IGSK-2 cells were positive against antihCG antibody and antiserotonin antibody, and negative against antisomatostatin antibody and antigastrin antibody.
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PMID:Establishment and characterization of an IGSK-2 cell line derived from ascitic fluid of recurrent hCG and somatostatin secreted adenocarcinoma of the stomach. 1754 19


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