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Trial of Best Supportive Care and Either Cisplatin or Paclitaxel to Treat Patients With Primary Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer and Inoperable Malignant Bowel Obstruction

ABSTRACT: The best way to treat MBO in patients with ovarian cancer has not been studied enough by trials that assess how more than one treatment arm (surgical, chemotherapeutic, supportive care approaches) affects clinical outcomes like resolution of bowel obstruction, survival, and quality of life. To improve patient outcomes, we must assess which patients will do better with palliative surgery, chemotherapy, or best supportive care. This study will gather safety information, and how reasonable it is to give chemotherapy and BSC to patients with advanced ovarian cancer and MBO who are non-surgical candidates. This study will also look into the effects of chemotherapy and BSC on the quality of life and resolution of bowel obstruction, in hopes to perform future studies that lead to the best management of MBO.

DISEASE(S): Ovarian Cancer,Peritoneal Neoplasms,Peritoneal Cancer,Bowel Obstruction,Fallopian Tube Neoplasms,Carcinoma, Ovarian Epithelial,Fallopian Tube Cancer,Ovarian Neoplasms,Intestinal Obstruction

PROVIDER: 2086061 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. Methods: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with the same standard platinum-based chemotherapy. Twelve patient tumors demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumors from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using a Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumors from the resistant group and the sensitive group. Results: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NFκB/ERK gene signalling networks. Conclusions: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials. Total RNA from 12 chemotherapy resistant and 16 sensitive chemotherapy sensitive high-grade serous epithelial ovarian cancer samples was subjected to whole transcriptome profiling using Affymetrix U133 Plus 2.0 arrays

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Trial of Best Supportive Care and Either Cisplatin or Paclitaxel to Treat Patients With Primary Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer and Inoperable Malignant Bowel Obstruction

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