Latest research and treatment of advanced-stage epithelial ovarian cancer

Abstract

The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics, despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free survival and overall survival, although the cure rates have been affected only modestly. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, growth in our armamentarium offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial 'ovarian' cancer and describes the direction and early results of clinical investigation.

Key Points

  • Ovarian cancer continues to be characterized by late-stage presentation and bulky intraperitoneal disease burden at presentation

  • Surgery and chemotherapy are the mainstays of primary therapy; 'optimal' surgical cytoreduction is being re-defined as resection of all macroscopic disease

  • Advances in adjuvant chemotherapy have leveraged intraperitoneal administration, dose-dense paclitaxel and the addition of biological agents predominately targeting angiogenesis

  • Maintenance therapy is a promising strategy as a primary or subsequent adjuvant approach, but as yet is not been proven to increase overall survival

  • Recurrence therapy has improved post-progression outcomes, although cures are elusive

  • Closely tied to a wider understanding of the underlying biology of ovarian cancer, drug development is increasingly focused on specific new targets in the hope of optimizing the therapeutic index

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Figure 1
Figure 2: Mutation profile of several genes represented against different ovarian cancer histologies.

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Acknowledgements

Portions of this work were supported by the Cancer Prevention & Research Institute of Texas (CPRIT,RP120214), NIH (P50 CA083639, P50 CA098258), Ovarian Cancer Research Fund Inc., The Marcus Foundation, and The Ann Rife Cox Chair in Gynecology (R. L. Coleman); NIH (CA109298, P50 CA083639, P50 CA098258, CA128797, RC2GM092599, U54 CA151668), the Ovarian Cancer Research Fund, Inc. (Program Project Development Grant), the DOD (OC073399, W81XWH-10-1-0158, BC085265), the RGK Foundation, the Gilder Foundation, the estate of C. G. Johnson Jr, the Marcus Foundation, the Blanton-Davis Ovarian Cancer Research Program, the Betty Anne Asche Murray Distinguished Professorship (A. K. Sood). The authors thank Robert Bristow for the image used in Figure 1.

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All the authors researched data for the article, made a substantial contribution to discussion of the content, wrote the article and edited it prior to submission.

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Correspondence to Robert L. Coleman.

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R. L. Coleman receives research funding from Amgen, AstraZeneca, Esperance Pharmaceuticals, Genentech/Roche, Merck, Millennium and Novartis. He on the Scientific Advisory Board of Abbott, BioMarin Pharmaceutical, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis Pharmaceuticals, GlaxoSmithKline, Johnson & Johnson, Morphotek/Easai and Nektar. B. J. Monk receives research funding from Novartis, Amgen, Genentech and Lilly; and is on the Speaker's Bureau of Roche/Genentech and Johnson & Johnson. He is also on the Scientific Advisory Board of Astellas, Array, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Qiagen and Roche/Genentech. T. J. Herzog receives research funding from Baye and is on the Scientific Advisory Board of Genentech/Roche, GlaxoSmithKline and Johnson & Johnson. A. K. Sood declares no competing interests.

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Coleman, R., Monk, B., Sood, A. et al. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol 10, 211–224 (2013). https://doi.org/10.1038/nrclinonc.2013.5

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