Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma.

Purpose: A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.

Patients And Methods: Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly.

Summary from the Kidney Cancer Association's Inaugural Think Thank: Coalition for a Cure.

Close to 74,000 cases of renal cell carcinoma (RCC) are diagnosed each year in the United States. The past 2 decades have shown great developments in surgical techniques, targeted therapy and immunotherapy agents, and longer complete response rates. However, without a global cure, there is still room for further advancement in improving patient care in this space.

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma.

Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR).

The role of inflammation in kidney cancer.

Renal cell carcinoma (RCC) constitutes more than 90 % of primary kidney tumors with the development of metastatic disease in the lung, bone, liver, and brain. Clear-cell RCC (CCRCC) is the most common histologic form of sporadic kidney cancer where the majority of tumors have inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene resulting in the accumulation of hypoxia-inducible factor (HIF) leading to dysregulation of cell growth and angiogenesis. Understanding of the genetic changes in RCC and the downstream events have led to the development of tyrosine kinase inhibitors (TKI) that target HIF-regulated proteins which currently represents front-line therapy for metastatic disease although resistance develops in most patients overtime.

The Cost of Hope: a candid roundtable discussion.

For Amanda Bennett and her husband Terence Foley, a 7-year battle with kidney cancer resulted in a price tag of more than $600,000, most of it spent in the final 2 years of his life. Ms. Bennett's memoir, The Cost of Hope, chronicles the couple's emotional struggle and the financial irrationality she uncovered when navigating the cancer continuum.

Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma.

Purpose: Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC.

Improvement in overall survival of patients with advanced renal cell carcinoma: prognostic factor trend analysis from an international data set of clinical trials.

Purpose: We assessed temporal shifts in the frequency of risk factors for patients with metastatic renal cell carcinoma in a multicenter, international data set.

Materials And Methods: An international database of 3,748 patients treated with systemic therapy for metastatic renal cell carcinoma from 1975 to 2002 was constructed by pooling clinical trial data. Proportions of previously identified risk factors were examined during 6 specified time cohorts.

Temsirolimus: a safety and efficacy review.

Introduction: The vascular endothelial growth factor (VEGF) pathway and the mammalian Target of Rapamycin (mTOR) represent the most frequently exploited targets in renal cell carcinoma (RCC). Temsirolimus is an inhibitor of mTOR, and is a unique ester derivative of sirolimus, a macrocyclic lactone, with improved pharmaceutical properties, including stability and solubility. Temsirolimus binds to the cytoplasmic protein FKBP-12, and the complex binds and inhibits mTOR.

Differing von hippel lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma.

In sporadic clear cell renal cell carcinoma (CCRCC), the von Hippel Lindau (VHL) gene is inactivated by mutation or methylation in the majority of primary (P) tumors. Due to differing effects of wild-type (WT) and mutant (MT) VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization analysis studies have reported genetic differences between paired P and metastatic (M) tumors.

Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma.

Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed.

Predicting responses to sunitinib using single nucleotide polymorphisms: Progress and recommendations for future trials.

Targeted therapy with tyrosine kinase inhibitors has led to a substantial improvement in the standard of care for patients with advanced or metastatic clear cell renal cell carcinoma. Because the mechanism of action, metabolism and transport of tyrosine kinase inhibitors can affect outcome and toxicity, several investigators have pursued the identification of single nucleotide polymorphisms (SNPs) in genes associated with these actions. We discuss SNPs associated with outcome and toxicity following sunitinib therapy and provide recommendations for future trials to facilitate the use of SNPs in personalized therapy for this disease.

Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents.

Prognostic model for survival in patients with metastatic renal cell carcinoma: results from the international kidney cancer working group.

Purpose: To develop a single validated model for survival in metastatic renal cell carcinoma (mRCC) using a comprehensive international database.

Experimental Design: A comprehensive database of 3,748 patients including previously reported clinical prognostic factors was established by pooling patient-level data from clinical trials. Following quality control and standardization, descriptive statistics were generated.

ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease.

Context: Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC).

Objective: This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms.

Evidence Acquisition: Medical literature was retrieved from PubMed up to April 2011.

Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib.

Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma.

Objective: To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-α2b (IFN-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab.

The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α.

Burden of metastatic bone disease from genitourinary malignancies.

Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life.

Clinical and immunomodulatory effects of bevacizumab and low-dose interleukin-2 in patients with metastatic renal cell carcinoma: results from a phase II trial.

Objective: Low-dose interleukin-2 (IL-2) is a historical treatment for metastatic renal cell carcinoma (mRCC). Increased vascular endothelial growth factor (VEGF) levels inhibit dendritic cell (DC) differentiation and augment production of immunosuppressive regulatory T (Treg) cells. Bevacizumab is an antibody that binds to VEGF, has activity in mRCC and may augment the anti-tumour immune effects of IL-2.

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab.

Background: Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab- or sunitinib-refractory mRCC have not been prospectively investigated.

Methods: Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study.

Safety and efficacy of sorafenib in elderly patients treated in the North American advanced renal cell carcinoma sorafenib expanded access program.

Objective: In this retrospective analysis of the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program in North America, we compared the safety and efficacy of sorafenib in patients aged ≥70 with those aged <70 years.

Methods: Patients were treated with oral sorafenib twice daily until the occurrence of disease progression or treatment intolerance. The primary objective of the ARCCS program was making sorafenib available to patients with advanced renal cell carcinoma (RCC) in the USA and Canada before marketing approval was obtained; the secondary objective was the evaluation of its safety and efficacy.

A phase II study of tandutinib (MLN518), a selective inhibitor of type III tyrosine receptor kinases, in patients with metastatic renal cell carcinoma.

Therapies which target VEGF and mTOR are now available for patients with metastatic renal cell carcinoma, but there is a continued need to develop agents for patients who become refractory to these initial agents. Tandutinib is a relatively selective inhibitor of type III tyrosine kinase receptor kinases with promising activity in some tumors. In this trial, 10 patients with metastatic renal cell carcinoma refractory to previous therapy with sunitinib or sorafenib (median age 61 years, 80% performance status 0, 60% intermediate MSKCC risk classification) received tandutinib 500 mg bid daily with RECIST-defined response as the primary endpoint and progression-free survival (PFS) and overall survival (OS) as secondary endpoints.