Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Sep 2004
ReviewPrevention of colorectal cancer through the use of COX-2 selective inhibitors.
Colorectal cancer is a major cause of morbidity and mortality accounting for an estimated 550,000 deaths annually worldwide. Colonic neoplasia develops in a stepwise fashion progressing from normal mucosa to adenomatous polyps to carcinoma, a process that takes years, thereby providing a prime opportunity for intervention. Although early detection by fecal occult blood testing and sigmoidoscopy can decrease the risk of cancer-related death by 20-30%, most persons never undergo appropriate screening. ⋯ Recent clinical studies using specific COX-2 inhibitors have shown that these compounds can: (1) reduce intestinal polyp burden in patients with familial adenomatous polyposis; (2) prevent the occurrence and/ or recurrence of colorectal adenomas and cancers; and (3) negatively regulate angiogenesis in colorectal cancer liver metastases. Compared to nonselective NSAIDs, COX-2 specific inhibitors cause substantially fewer gastrointestinal side effects. These findings indicate that a widely used and relatively safe class of drugs may represent a viable and effective anticancer strategy for a disease that causes over a half-million deaths per year.
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Cancer Chemother. Pharmacol. · Sep 2004
ReviewIntegration of novel agents in the treatment of colorectal cancer.
Two of the most promising new targets in the treatment of colorectal cancer are the epithelial growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). Agents that inhibit the EGFR or bind to VEGF have demonstrated clinical activity as single agents and in combination with chemotherapy in phase II and phase III clinical trials. The most promising of these agents are cetuximab, which blocks the binding of EGF and transforming growth factor alpha (TGF-alpha) to EGFR, and bevacizumab, which binds free VEGF. ⋯ It was the first large, randomized, phase III survival trial to assess the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Integration of novel agents targeting VEGF and EGFR with irinotecan-based chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. The goal in the future will be to predict which specific chemotherapy and targeted agent combination will most likely benefit individual patients.
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Cancer Chemother. Pharmacol. · Sep 2004
ReviewImatinib mesylate acts in metastatic or unresectable gastrointestinal stromal tumor by targeting KIT receptors--a review.
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. This tumor is resistant to conventional chemotherapy and radiotherapy. ⋯ Although imatinib mesylate has been used in GIST treatment for several years, its use marks a new era of molecular targeting therapy. While several issues remain, they should be clarified by the current clinical trials and associated laboratory studies.
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Cancer Chemother. Pharmacol. · Sep 2004
ReviewAdjuvant chemotherapy for gastric cancer in Japan: global and Japanese perspectives.
Adjuvant therapy for gastric cancer after surgical resection has been under clinical investigation for decades. However, up until now, consistent and concrete evidence has not been generated either in Japan or other countries in favor of adjuvant therapy in terms of survival compared to surgery alone. Meta-analyses reported from Western countries have shown either no or borderline benefit for chemotherapy after surgical resection of gastric cancer. ⋯ A pooled analysis of the two preceding trials showed a borderline survival benefit for o-FP compared to surgery alone. If o-FP treatment shows a 5% difference in survival benefit in the NSAS-GC trial, a meta-analysis of the three trials would probably reveal overall significant results. In conclusion, this therapy could become the standard adjuvant treatment regimen for gastric cancer patients after curative resection in Japan.
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Cancer Chemother. Pharmacol. · Sep 2004
Clinical TrialPharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
To determine the pharmacokinetics of adaptively dosed carboplatin when administered in combination with the bradykinin agonist, lobradimil (RMP-7, Cereport), to pediatric patients with brain tumors. ⋯ Adaptive dosing of carboplatin based on GFR overestimated the dose required to achieve the target carboplatin AUC in pediatric patients with brain tumors treated with concurrent lobradimil. The degree to which the measured carboplatin AUC exceeded the target AUC appeared to be greater at higher doses of lobradimil, suggesting that the failure of the adaptive dosing method was related to an unexpected pharmacokinetic drug interaction.