Renal cell carcinoma - PubMed (original) (raw)

Review

Renal cell carcinoma

Eric Jonasch et al. BMJ. 2014.

Abstract

The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC.

© BMJ Publishing Group Ltd 2014.

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Conflict of interest statement

Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests. EJ: consultant for Aveo, Bayer, GSK, Novartis, and Pfizer; clinical research support from BMS, GSK, Novartis, Pfizer, and Onyx; laboratory research support from Exelixis. WKR: consultant for Aveo (uncompensated), clinical research support from GSK and Seattle Genetics. ); WKR’s husband was funded for a research sabbatical by Novartis pharmaceuticals. JJG: none.

Figures

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Fig 1 Incidence of renal cell carcinoma in different geographical regions. Adapted with permission from Cancer Research UK

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Fig 2 Which continent has the highest incidence of kidney cancer? Use our interactive tool to find out how cancer incidence varies by population. See

www.bmj.com/content/349/bmj.g4797/infographic

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Fig 3 Tumor node metastasis (TNM) staging for renal cell carcinoma (2010 version)

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Fig 4 Memorial Sloan Kettering risk criteria. The algorithm includes five factors: hemoglobin below the lower limit of normal, Karnofsky performance status of less than 80, less than one year from diagnosis to start of systemic therapy, corrected calcium above the upper limit of normal, and lactate dehydrogenase more than 1.5 times the upper limit of normal. Patients with a good risk have no risk factors; intermediate risk patients have one or two; and poor risk patients have three or more factors

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Fig 5 Kinome profile for axitinib, pazopanib, sunitinib, and sorafenib. The branches represent the known human kinases. Red circles represent targets for the various agents and the size of the circle indicates the inhibitory potency of the kinase (circle sizes are inversely proportional to fold selectivity ratios). Axitinib is an example of a highly specific kinase inhibitor, whereas sunitinib has a considerably broader range of action. Darker red dots provide contrast where overlapping dots are present. Adapted, with permission, from McTigue and colleagues

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Fig 6 Overall survival in patients who developed (A) treatment emergent systolic hypertension (>140 mm Hg) and (B) treatment emergent diastolic hypertension while receiving sunitinib. Those who developed hypertension had significantly better overall survival than those who did not. Adapted, with permission, from Rini et al

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