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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Docetaxel has been evaluated in six tumour types in a total of 189 patients entered into phase II studies. Treatment consisted of a 1 h intravenous infusion of docetaxel 100 mg/m2 repeated every 3 weeks. No premedication was administered for possible hypersensitivity reactions. Docetaxel was found to be effective as first-line chemotherapy for head and neck cancer (response rate 44%) gastric cancer (23%) and melanoma (14%) and as second-line chemotherapy for soft tissue sarcomas (21%; 95% confidence interval: 7.5%-43.7%). The results in colorectal and renal cancer were disappointing, with response rates of less than 10%. The most frequent adverse effects were alopecia (81%), grade III-IV leukocytopenia of short duration (66%) and skin reactions (52%). Hypersensitivity reactions were mild and occurred in 26% of patients. Docetaxel is an important new drug in the treatment of solid tumours.
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PMID:Phase II studies of docetaxel in the treatment of various solid tumours. EORTC Early Clinical Trials Group and the EORTC Soft Tissue and Bone Sarcoma Group. 757 1

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

Paclitaxel has shown a significant activity on esophageal cancer in a phase II trial. Irinotecan has established the single-agent efficacy on both gastric and colorectal cancer. Docetaxel has attained a significant activity on advanced gastric cancer and a 29% response rate on pancreatic cancer in a phase II trial. Tomudex has shown comparable activity to leucovorin and 5-fluorouracil in colorectal cancer.
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PMID:New systemic drugs in the treatment of gastrointestinal cancer. 886 7

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently in phase II/III clinical trial. We found that the sensitivity to taxotere was correlated with apoptotic cell death determined by the internucleosomal DNA ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA ladders by taxotere was significant, respectively (p<0.05). The introduction of bcl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP-16 and taxotere 2-3-fold in the IC50 values, whereas the introduction of bax gene increased the sensitivity to CDDP, VP-16 and taxotere 2-5-fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mRNA overexpression of bax gene was found in the bcl-Xs-transfected cells. Likewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-transfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a crucial role in modulating apoptotic cell death in the sensitivity to anticancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating downstream signals leading to apoptosis in gastric cancer cells.
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PMID:Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells. 1049 58

We conducted a phase II study to evaluate the efficacy and tolerance of docetaxel monotherapy with granulocyte colony-stimulating factor (G-CSF) support in patients with advanced gastric cancer. Thirty patients with measurable advanced gastric cancer were enrolled. Twenty-four patients were chemotherapy-naive and six patients had previously received adjuvant chemotherapy after complete surgical resection. Docetaxel was administered at 100 mg/m2 IV during 1 hour every 3 weeks. G-CSF 5 microg/kg SC was also given on days 2 through 8 prophylactically to all patients. All patients were evaluable for response and toxicity. We observed one complete and five partial responses for an overall response rate of 20% (95% confidence interval: 6-34%). In addition, seven patients (23%) had stable disease. After a median follow-up time of 7 months, the median duration of response was 4.5 months, the median time of tumor progression was 6 months, and the median survival was 7 months. The estimated probability of 1-year survival was 28%. Toxicity was generally mild. Grade III/IV neutropenia occurred in 11 (36%) patients. Neutropenia with fever developed in three patients (10%). There were no toxic deaths. Docetaxel with G-CSF support is an active drug and well tolerated by patients with advanced gastric cancer. Docetaxel merits further investigation in combination with other active agents as frontline treatment in patients with advanced gastric cancer.
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PMID:Frontline treatment of advanced gastric cancer with docetaxel and granulocyte colony-stimulating factor (G-CSF): a phase II trial. 1095 59

Metastatic gastric cancer is a relatively chemosensitive disease. With current regimens, 25% to 40% of patients can be expected to respond, and median survival of 6 to 8 months is achievable. These outcomes may be improved by the use of infusional fluorouracil (5-FU) in combination with cisplatin (Platinol) or the newer agents docetaxel (Taxotere) and irinotecan (Camptosar). Phase II studies using these approaches have reported response rates of 50% to 60% and median survival of 11 months. Chemotherapy may also have a role in earlier stages of gastric cancer. However, the value of adjuvant therapy in improving survival following successful resection has still to be demonstrated, as has the survival benefit of preoperative treatment. Nevertheless, primary chemotherapy has demonstrated a capacity to downstage disease in certain otherwise inoperable cases.
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PMID:Developments in the treatment of gastric cancer in Europe. 1120 Jan 44

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.
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PMID:A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer. 1120 39

Standard chemotherapy for advanced gastric cancer remains undefined. Two of the most popular regimens-ECF [epirubicin-cisplatin-5-fluorouracil (5-FU)] and PELF (cisplatin-epirubicin-5-FU-leucovorin)-have been shown to be active, but each has limitations. Phase II trials show that single-agent docetaxel is an active agent in advanced gastric cancer, producing overall response rates (ORRs) of 17.5-24%. Docetaxel has also been shown to lack cross-resistance with other drugs in gastric cancer, and is likely to be at least additive to cisplatin and 5-FU. Phase II results of docetaxel combinations in advanced gastric cancer are encouraging. Docetaxel-cisplatin has yielded response rates similar to those achieved by ECF and PELF. Adding 5-FU to docetaxel-cisplatin has achieved an ORR of 52 versus 45% for docetaxel-cisplatin in a randomized phase II trial. Docetaxel-based regimens demonstrate acceptable tolerability despite predictable hematotoxicity. Neutropenia, the major toxicity, is manageable by dose modification or by using prophylactic granulocyte colony stimulating factor. Several phase III trials are now ongoing, including a large-scale trial of docetaxel-cisplatin-5-FU versus cisplatin-5-FU. Results will show whether docetaxel improves overall response and survival, as suggested in the phase II setting.
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PMID:Docetaxel in advanced gastric cancer. 1204 56

Docetaxel (Taxotere) has been successfully investigated in the therapy for advanced gastroesophageal tumors as both a single agent and in combination regimens. As a single agent, phase II study results demonstrate an overall response rate of 17% to 24%, with occasional complete responses in a disease in which complete responses are rare. These figures classify docetaxel among the most active agents for the disease. Further research initiatives in gastric cancer have evaluated the combined use of docetaxel with traditionally established agents, such as cisplatin and fluorouracil (5-FU). The rationales for the combined use of docetaxel with these agents include the in vitro demonstration of a lack of complete cross-resistance and nonoverlap-ping side-effect profiles. Phase II study results of docetaxel-based combinations demonstrate high overall response rates and progression-free survival, comparable with results obtained with established three- and four-drug regimens. Therapy is generally well tolerated, with a predominant toxicity of hematologic neutropenia. Docetaxel-based combination regimens are currently undergoing evaluation in randomized phase III trials in comparison with established standard regimens. While previous combination chemotherapy regimens have failed to improve survival over single-agent therapy, the aim for incorporation of docetaxel with other active agents is to improve palliation and possibly survival of patients with gastric cancer.
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PMID:Docetaxel for gastric and esophageal carcinomas. 1210 2

Docetaxel is considered to be active in untreated and previously treated patients with gastric carcinoma. In a multinational phase II trial (TAX 325), 158 untreated patients with advanced gastric cancer (99% without prior chemotherapy) were randomized to receive, every 3 weeks, either docetaxel 85 mg/m2 plus cisplatin 75 mg/m2 (TC) or docetaxel 75 mg/m2 plus cisplatin 75 mg/m2, plus a 5-day continuous infusion of 750 mg/m2 5-fluorouracil (FU; TCF). By intent-to-treat analysis, patients receiving TCF had a significantly higher response rate and longer time to progression. Overall survival in the two arms was not significantly different. Toxicity (particularly gastrointestinal toxicity) was greater with the TCF combination than in the TC arm, and there was a greater need for dose reduction. However, adverse events in both arms were manageable and there were no deaths associated with either regimen. Following these findings, a phase III trial comparing a control arm of cisplatin plus 5-FU against an experimental arm consisting of the TAX 325 phase II docetaxel/cisplatin/5-FU regimen is now in progress.
Gastric Cancer 2002
PMID:Docetaxel in combination for advanced gastric cancer. 1277 85


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