Ovarian Cancer Pharmacogenetics

卵巢癌药物遗传学

• 批准号: 6899926
• 负责人: HOWARD L MCLEOD
• 金额: $ 15.76万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899926
• 关键词: antineoplastics; clinical research; drug screening /evaluation; female; gene expression; genotype; human subject; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; ovary neoplasms; paclitaxel; pharmacogenetics; pharmacokinetics; platinum; single nucleotide polymorphism; women' s health

DESCRIPTION (provided by applicant): It is an exciting time for the treatment of ovarian cancer. The availability of multiple therapeutic options with clear antitumor activity requires clinical decisions to be made for individual patients and these decisions are best made with quantitative information. However, there are currently insufficient tools to guide the selection of therapy for ovarian cancer. The recently completed SCOTROC1 Phase III clinical trial compared paclitaxel/carboplatin and docetaxel/carboplatin, with a 29% complete response rate observed in both arms. The incidence and type of toxicity differed significantly between the two therapies. This offers the opportunity to apply human genomic information to develop predictive markers to guide therapy selection. Therefore, this project will address the following Specific Aims: 1. Determine the predictive impact of variants in taxane/platinum candidate genes on severe toxicity in patients on the SCOTROC1 study. 2. Define the association of genetic variants in taxane/platinum candidate genes with tumor response and progression-free survival after treatment for ovarian cancer. 3. Identify genotypes associated with favorable risk-benefit for taxane/platinum therapy in ovarian cancer. This study will take advantage of DNA collected from 914 patients on the SCOTROC1 Phase III clinical trial. Samples from both treatment arms will be assessed for the presence of multiple polymorphisms in genes of relevance to taxane and platinum activity and efficacy. Single polymorphism and haplotype associations with toxicity and response will be performed to address Specific Aims 1-3. The availability of uniform information on toxicity, tumor response, and patient survival makes this study a powerful framework with which to answer pharmacogenetic questions. Significant associations will provide the basis for future genotype-directed clinical trials in ovarian cancer.

描述（由申请人提供）：对于卵巢癌的治疗来说，这是一个激动人心的时刻。具有明确抗肿瘤活性的多种治疗选择的可用性需要针对个体患者做出临床决策，并且这些决策最好利用定量信息来做出。然而，目前没有足够的工具来指导卵巢癌治疗方法的选择。最近完成的 SCOTROC1 III 期临床试验比较了紫杉醇/卡铂和多西紫杉醇/卡铂，两组的完全缓解率为 29%。两种疗法之间的毒性发生率和类型显着不同。这提供了应用人类基因组信息来开发预测标记来指导治疗选择的机会。因此，该项目将解决以下具体目标： 1. 在 SCOTROC1 研究中确定紫杉烷/铂候选基因变异对患者严重毒性的预测影响。 2. 确定紫杉烷/铂候选基因中的遗传变异与卵巢癌治疗后肿瘤反应和无进展生存期的关联。 3. 确定与卵巢癌紫杉烷/铂治疗有利风险效益相关的基因型。这项研究将利用从 SCOTROC1 III 期临床试验中收集的 914 名患者的 DNA。将评估两个治疗组的样本是否存在与紫杉烷和铂活性和功效相关的基因的多重多态性。将进行单一多态性和单倍型与毒性和反应的关联，以解决具体目标 1-3。关于毒性、肿瘤反应和患者生存的统一信息的可用性使这项研究成为回答药物遗传学问题的强大框架。显着的关联将为未来卵巢癌基因型导向的临床试验提供基础。