Dataset Information

Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach.

ABSTRACT: The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma (mRCC) in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.

SUBMITTER: Shinder BM

PROVIDER: S-EPMC5449498 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach.

Shinder Brian M BM Rhee Kevin K Farrell Douglas D Farber Nicholas J NJ Stein Mark N MN Jang Thomas L TL Singer Eric A EA

Frontiers in oncology 20170531

The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoad ...[more]

PMID: 28620578

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Project description:In recent years, targeted agents have changed the treatment landscape for patients with advanced renal cell carcinoma (RCC), greatly improving treatment outcomes. Several targeted agents are now licensed for the treatment of metastatic RCC (mRCC), and a number of new agents are under investigation. Axitinib, a small molecule indazole derivative is an oral, potent multitargeted tyrosine kinase receptor inhibitor, which selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 at subnanomolar concentrations, in vitro. In various nonclinical models, axitinib has demonstrated in vivo target modulation and antiangiogenesis. In pharmacokinetic studies, axitinib administered orally with food at the proposed regimen of 5?mg twice daily continuous daily dosing, is rapidly absorbed, reaching peak concentrations within 2-6 hours. Axitinib is metabolized primarily in the liver via the cytochrome P450 (CYP) system with less than 1% of the administered drug passing unchanged in the urine. The pharmacokinetics of axitinib do not appear to be altered by coadministered chemotherapies, and antacids do not have a clinically significant effect. However, coadministration with CYP3A4 and 1A2 inducers is contraindicated. In addition, proton pump inhibitors reduce the rate of axitinib absorption. Increased axitinib exposure is associated with higher efficacy indicated by decreased tumor perfusion and volume. In three phase II clinical trials in patients with advanced RCC previously treated with cytokines, chemotherapy or targeted agents, axitinib has demonstrated antitumor activity with a favorable non-cumulative toxicity profile. In one study of Western patients with cytokine-refractory mRCC, an objective response rate (ORR) of 44.2% (95% CI 30.5, 58.7) was achieved. The median time to progression was 15.7 months (95% CI 8.4, 23.4) and the median overall survival (OS) was 29.9 months (95% CI 20.3, not estimable). In the second study of patients with sorafenib-refractory mRCC, ORR was 22.6% (95% CI 12.9, 35.0). The median progression-free survival (PFS) was 7.4 months (95% CI 6.7, 11.0) and a median OS of 13.6 months (95% CI 8.4, 18.8) was achieved. Results from the third study in Japanese patients with cytokine-refractory mRCC reported an ORR of 55% and median PFS of 12.9 months (95% CI 9.8, 15.6). In the three studies, the most common adverse events reported were fatigue, hypertension, hand-foot syndrome (HFS), and gastrointestinal toxicity, which were generally manageable with standard medical intervention. Of note, the incidence of HFS and proteinuria in the Japanese study was higher than that reported in the Western study in cytokine-refractory mRCC patients. An observed association between diastolic blood pressure ?90?mmHg and increased efficacy suggests potential use as a prognostic biomarker. However, this requires further investigation. Two randomized phase III clinical trials are ongoing to determine the efficacy of axitinib in patients with mRCC in the first- and second-line setting. These results will help to determine the place of axitinib in the mRCC treatment algorithm.

Project description:BACKGROUND:Pazopanib is indicated in the first-line treatment of metastatic renal cell cancer (mRCC). The aim of this study was to review the efficacy, safety, and pharmacokinetics of pazopanib and see how these aspects are linked to clinical practice. METHODS:A non-exhaustive systematic review was conducted according to the three topics. No publication restrictions were imposed and the selected languages were Spanish and English. After that, a summary of the main results and findings of the review was presented and discussed during three meetings (one for each topic) with 13 medical oncologists that usually treat mRCC. At these meetings, a questionnaire on the first-line use of pazopanib in clinical practice was also drawn up. After the meetings, the questionnaire was completed by 60 specialist medical oncologists in renal cancer. RESULTS:The efficacy and safety of pazopanib have been demonstrated in several clinical trials, and subsequently confirmed in studies in real-world clinical practice. In addition to its clinical benefit and good safety profile, quality of life results for pazopanib, which compare favorably to sunitinib, make it a good option in the first-line treatment of patients. Special populations have been included in studies conducted with pazopanib, and it is safe for use in elderly patients, poor functional status, kidney failure, and mild or moderate hepatic impairment, and in patients with concomitant cardiovascular disease. The results of the questionnaire have shown that pazopanib is perceived as an effective drug, in which quality of life (QoL) outcomes are valued above all. CONCLUSIONS:This paper offers a comprehensive and critical summary of efficacy, tolerability, and pharmacokinetics of pazopanib in the treatment of mRCC. Pazopanib is an effective treatment with an acceptable safety profile. Its QoL and tolerability results offer certain advantages when compared with other therapeutic alternatives, and its use appears to be safe in different patient profiles.

Dataset Information

Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach.

Publications

Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach.

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