Platinum-based chemotherapy for variant castrate-resistant prostate cancer.

Purpose: Clinical features characteristic of small-cell prostate carcinoma (SCPC), "anaplastic," often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined "anaplastic" clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy.

Experimental Design: A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity.

Radiofrequency ablation of renal tumours with clinical, radiographical and pathological results.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Radiological imaging is heavily relied on for follow up after renal ablative therapy. We show that while this is largely reliable, there are quantifiable false negative and false positive findings. A non-involuting zone of ablation should be considered for multisite-directed core biopsies even in the absence of detectable enhancement.

Illness uncertainty and quality of life of patients with small renal tumors undergoing watchful waiting: a 2-year prospective study.

Background: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL.

Objective: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass.

Energy balance, polymorphisms in the mTOR pathway, and renal cell carcinoma risk.

Background: The interplay between obesity, physical activity, weight gain, and genetic variants in the mTOR pathway has not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity, and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association.

Development of accurate models for individualized prediction of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

Background: There is limited evidence to guide patient selection for cytoreductive nephrectomy (CN) following the diagnosis of metastatic renal cell carcinoma (mRCC).

Objective: Given the significant variability in oncologic outcomes following surgery, we sought to develop clinically relevant, individualized, multivariable models for the prediction of cancer-specific survival at 6 and 12 mo after CN. The development of this nomogram will better help clinicians select patients for cytoreductive surgery.

VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue.

Summary: We developed a new algorithmic method, VirusSeq, for detecting known viruses and their integration sites in the human genome using next-generation sequencing data. We evaluated VirusSeq on whole-transcriptome sequencing (RNA-Seq) data of 256 human cancer samples from The Cancer Genome Atlas. Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity.

The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma.

Objectives: This study evaluated the effect of tyrosine kinase inhibitors (TKIs) on the brain metastasis (BM), local control (LC), and overall survival (OS) of patients with renal cell carcinoma (RCC) with BM.

Methods: A retrospective review of patients with RCC BM was conducted. Eligible patients from 2 eras: pre-TKI, 2002 to 2003 and post-TKI, 2006 to 2007, were identified.

Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.

Purpose: Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways.

Methods: Patients with metastatic RCC (n = 217) were prospectively enrolled in this study.

A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma.

Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC).

Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC.

Phase II trial of pemetrexed plus gemcitabine in patients with locally advanced and metastatic nonclear cell renal cell carcinoma.

Objective: To determine the clinical activity and safety of the combination of pemetrexed and gemcitabine in advanced nonclear cell renal cell carcinoma (nccRCC).

Methods: In this phase II study, patients received pemetrexed 500 mg/m intravenous infusion over 10 minutes on day 1 followed immediately by gemcitabine 1500 mg/m intravenously over 30 minutes on day 1, with cycles repeated every 14 days. Planned enrollment was 40 patients.

AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 study.

Background: This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study.

Methods: Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression.

Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases.

Unlabelled: Study Type--Diagnostic (cohort) Level of Evidence: 2b. What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC.

Outcome of patients with renal cell carcinoma metastatic to the brain treated with sunitinib without local therapy.

Objective: To assess the response of brain metastases to sunitinib in patients with renal cell carcinoma (RCC) who did not undergo prior surgical resection or radiation to the brain.

Methods: We retrospectively reviewed the medical records of adult RCC patients who had metastases to the brain and received sunitinib.

Results: Six patients with clear-cell RCC were identified between March 2006 and August 2009.

Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall.

Renal medullary carcinoma (RMC) is a rare aggressive renal tumor that classically afflicts young black patients with sickle cell trait. The tumor shows overlapping pathologic and clinical characteristics with collecting duct carcinoma and urothelial carcinoma, which often results in a diagnostic conundrum. When the tumor presents in a metastatic site in the absence of a history of renal tumor, germ-cell tumor is often a primary diagnostic consideration, given the young age of most patients.

Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.

Background: Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue.

Methods: Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off.

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure.

Purpose: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.

Materials And Methods: This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function.

Pilot trial of bone-targeted therapy combining zoledronate with fluvastatin or atorvastatin for patients with metastatic renal cell carcinoma.

Background: The biological rationale for this study came from the observation that bisphosphonates and statins affect bone metastasis in different ways and thus combination therapy may provide synergistic benefit. This pilot trial evaluated the efficacy and safety of combining a bisphosphonate and a statin in patients with RCC metastatic to bone.

Methods: Patients with RCC and bone metastasis received zoledronate and fluvastatin or atorvastatin.

Adjuvant and neoadjuvant therapy in renal cell carcinoma.

Nephrectomy continues to be the cornerstone of treatment for localized renal cell carcinoma (RCC). Despite undergoing nephrectomy, recurrence of disease remains a concern in many patients, and different medical therapies are being investigated as means to decrease this risk. The use of the traditional immunotherapy options has not provided benefit as adjuvant treatment in this disease state.

Emerging targeted therapies in metastatic renal cell carcinoma.

Insights into renal cell carcinoma (RCC) biology have greatly expanded the treatment armamentarium for metastatic RCC (mRCC). Since 2005, six targeted agents have been approved by the US Food and Drug Administration (FDA) for the management of mRCC, and many new targeted therapies are in development. A number of novel VEGF Inhibitors/Multi-Tyrosine Kinase Inhibitors are currently in various stages of development.

Treatment-related optimism protects quality of life in a phase II clinical trial for metastatic renal cell carcinoma.

Background: Patients on clinical trials often experience declining quality of life (QOL). Little is known about the psychosocial variables that buffer against decline.

Purpose: This study aims to examine correlations between psychosocial variables and QOL over the course of a clinical trial in patients with metastatic renal cell cancer.

Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib.

Background: In metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown.

Objective: To evaluate whether early PT size reduction is associated with improved OS in patients with mRCC undergoing treatment with sunitinib.

Design, Setting, And Participants: We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between January 2004 and December 2009 without prior systemic treatment who received sunitinib with their PT in situ.

Systemic therapy for metastatic non-clear-cell renal cell carcinoma: recent progress and future directions.

Insights into the biology of clear-cell renal cell carcinoma (CCRCC) have identified multiple pathways associated with the pathogenesis and progression of this cancer. This progress has led to the development of multiple agents targeting these pathways, including the tyrosine kinase inhibitors sorafenib, sunitinib, and pazopanib, the monoclonal antibody bevacizumab, and the mTOR inhibitors temsirolimus and everolimus. With the exception of temsirolimus, phase 3 trials tested these agents in patients with clear-cell histology; therefore, their efficacy in non-CCRCC is unclear.