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.
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