Circulating biomarkers for vascular endothelial growth factor inhibitors in renal cell carcinoma.

In recent years, there has been significant progress in the clinical development and application of antiangiogenic therapies in renal cell carcinomas, particularly inhibitors of the vascular endothelial growth factor (VEGF) pathway. Despite this progress, no validated methods are currently available for identifying which patients are most likely to respond to treatment or experience toxic effects, selecting the optimal dose, or determining whether the intended molecular target has been effectively inhibited. However, recent studies have suggested that some of the biomarkers currently under investigation in clear cell renal cell carcinoma for VEGF pathway inhibitors are promising.

Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma.

Objective: To prospectively establish objective selection criteria for metastasectomy in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: Between 1991 and 1999, 38 patients with mRCC with responsive or stable disease after initial systemic therapy, and with potentially resectable disease, were enrolled. Patients had a metastasectomy with curative intent and received consolidative adjuvant systemic therapy.

Patterns of disease progression in metastatic renal cell carcinoma patients treated with antivascular agents and interferon: impact of therapy on recurrence patterns and outcome measures.

Background: : The standard of care for patients with advanced renal cell carcinoma (RCC) has changed to favor targeted therapy over immunotherapy. Differences in patterns of progression between patients treated with these 2 modalities, and the impact of disease stabilization on outcome, were investigated.

Methods: : Patients who progressed on first line antivascular therapy (AVT) or interferon were identified, and their medical records reviewed.

Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib.

Background: Sorafenib-induced dermatologic toxicity is common and consists primarily of dry skin, maculopapular rash, hand-foot skin reaction, and alopecia. Cutaneous squamous cell carcinoma (SCC) and inflammation of actinic keratosis (AK) were reported in 2 patients treated with sorafenib (Lacouture et al), but the scope of this observation has not been evaluated.

Patients And Methods: We reviewed medical records of 131 patients with metastatic renal cell carcinoma treated with single-agent sorafenib at our institution from June 1, 2005, through April 4, 2007.

Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.

Purpose: p27 localization and expression has prognostic and predictive value in cancer. Little is known regarding expression patterns of p27 in renal cell carcinoma (RCC) or how p27 participates in disease progression or response to therapy.

Experimental Design: RCC-derived cell lines, primary tumors, and normal renal epithelial cells were analyzed for p27 expression, phosphorylation (T157 of the NLS), and subcellular localization.

Inhibition of Mxi1 suppresses HIF-2alpha-dependent renal cancer tumorigenesis.

In clear cell renal cancers, the primary molecular defect is inactivation of the von Hippel-Lindau (VHL) gene. Loss of pVHL, the VHL gene product, leads to constitutive activation of hypoxia-inducible factor (HIF) signaling. While downregulation of HIF suppresses tumor formation by pVHL-defective renal carcinoma cells, the relative contribution of individual HIF regulated genes to HIF-dependent tumorigenesis remains under investigation.

Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors.

Context: von Hippel-Lindau disease is characterized by highly vascularized tumors of multiple organs.

Evidence Acquisition: We present a patient with von Hippel-Lindau disease with multiple renal and pancreatic tumors and a malignant pheochromocytoma infiltrative of the sacrum and associated with lymph nodule metastases. The pheochromocytoma expressed high protein level of vascular endothelial growth factor and platelet-derived growth factor-beta receptor.

Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma.

Objectives: To evaluate the effect of adjuvant thalidomide on recurrence-free survival (RFS) after nephrectomy for high-risk metastatic renal cell carcinoma (RCC).

Methods: Eligibility criteria for enrollment on this randomized trial included any histologic subtype, T2 (high grade, any N), T3/T4 (any grade, any N), or node-positive (any grade, any T) RCC. We randomized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months.

Adjuvant and neoadjuvant therapy in renal cell carcinoma.

A number of patients with renal cell carcinoma (RCC) are faced with the knowledge that, despite undergoing nephrectomy, they have a substantial risk of disease recurrence. Prior efforts to decrease recurrence risk using immunotherapy have largely been ineffective. The reasons for the failure of immunotherapy are not clear, as our ability to measure immunological outcomes has not provided us with clues on the determinants which signal a successful antitumor effect.

Current status of debulking nephrectomy in the era of tyrosine kinase inhibitors.

Cytoreductive nephrectomy (CN) has an established role against metastatic renal cell carcinoma (mRCC) in properly selected patients and offers a survival advantage when performed prior to cytokine therapy. With the emergence of new, effective targeted molecular therapies for mRCC, well-designed prospective trials are needed to clarify the biologic effects of CN to determine when and for whom CN should be performed in the context of targeted systemic therapy. Consequently, a thorough characterization of the systemic effects afforded by CN is imperative for developing individualized treatment strategies that effectively address the underlying biology of mRCC while maximizing patient quality of life during therapy.

A phase II trial of gemcitabine plus capecitabine for metastatic renal cell cancer previously treated with immunotherapy and targeted agents.

Purpose: We assessed the clinical activity and safety of gemcitabine plus capecitabine in patients with metastatic renal cell cancer previously treated with immunotherapy.

Materials And Methods: In this phase II trial patients received 1,000 mg/m(2) gemcitabine intravenously on days 1, 8 and 15, plus 830 mg/m(2) capecitabine orally twice daily on days 1 to 21 of 28-day cycles. The primary end point was progression-free survival time.

A novel von Hippel-Lindau point mutation presents as apparently sporadic pheochromocytoma.

Von Hippel Lindau disease is a common cause of apparently sporadic pheochromocytomas. Herein, we describe a 20-year-old man with an apparently sporadic pheochromocytoma associated with a novel, relatively conservative germline Gly104Val VHL gene mutation, which is localized within exon 1 of the VHL gene corresponding to the beta -domain of the VHL protein (pVHL). The nearly asymptomatic patient's father also carries the same mutation.

Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurrent renal cell carcinoma.

Purpose: Targeted molecular therapies such as bevacizumab, sunitinib and sorafenib before surgical resection hold promise as rational treatment paradigms for patients with metastatic or locally recurrent renal cell carcinoma. To analyze the safety of this approach we evaluated surgical parameters and perioperative complications in patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of retroperitoneal renal cell carcinoma recurrence, and compared them to a matched patient cohort who underwent up-front surgical resection.

Materials And Methods: We evaluated surgical parameters and perioperative complications in 44 patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of local renal cell carcinoma recurrence, and in a matched cohort of 58 patients who underwent up-front surgery.

Patterns of intervention for renal lesions in von Hippel-Lindau disease.

Objective: To review the records of patients at our centre with von Hippel-Lindau (VHL) disease, to determine the incidence of renal cell carcinoma (RCC) and patterns of intervention using minimally invasive therapies.

Patients And Methods: Patients with genetically confirmed VHL were evaluated in a multidisciplinary clinical care centre established in 2003. Patients were preferentially offered percutaneous radiofrequency ablation (RFA).

Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma.

Background: Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron-binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine-activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types.

Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings.

The aim of this study was to evaluate the clinical efficacy as determined by time to progression and response rate (RR) of autologous vitespen (formerly HSPPC-96; Oncophage, Antigenics Inc., New York, NY, USA) with and without interleukin-2 (IL-2; Proleukin: Chiron, Emoryville, CA, USA) in stage IV metastatic renal cell carcinoma (RCC) patients undergoing nephrectomy. Eighty-four patients were enrolled on study, and then underwent nephrectomy and harvest of tumour tissue for use in autologous vaccine manufacture.

Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology.

Purpose: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D.

Cytoreductive nephrectomy for T4NxM1 renal cell carcinoma: the M.D. Anderson Cancer Center experience.

Objectives: Although cytoreductive nephrectomy may provide a survival benefit in metastatic renal cell carcinoma, patients with locally advanced lesions may be denied cytoreduction because of a perceived worse outcome and increased morbidity. We reviewed our experience with cytoreductive nephrectomy in patients with contiguous organ involvement (Stage T4NxM1) to evaluate the outcome and morbidity.

Methods: From 1993 to 2004, 498 patients underwent cytoreductive nephrectomy for renal cell carcinoma.

Cytoreductive nephrectomy in the elderly patient: the M. D. Anderson Cancer Center experience.

Purpose: Cytoreductive nephrectomy as part of a multidisciplinary approach may be considered in patients with metastatic renal cell carcinoma. The benefit in the elderly population (75 years or older) is unclear. We reviewed our experience to help determine if it is of benefit in this patient population.

Presurgical therapy in metastatic renal cell carcinoma.

The standard approach for managing patients with metastatic renal cell carcinoma consists of a cytoreductive nephrectomy followed by immunotherapy, chemotherapy or a targeted agent. Optimal timing of surgery and systemic therapy is not known, and has not been researched. A number of questions arise.

Improved tolerability and quality of life with maintained efficacy using twice-daily low-dose interferon-alpha-2b: results of a randomized phase II trial of low-dose versus intermediate-dose interferon-alpha-2b in patients with metastatic renal cell carcinoma.

Background: In vivo data have shown a more potent antiangiogenic effect and a higher antitumor activity of low-dose interferon (IFN) given twice daily. In a randomized Phase II trial, the authors tested the hypothesis that twice-daily low-dose IFN is more effective than daily intermediate-dose IFN in patients with metastatic renal cell cancer (MRCC).

Methods: A total of 118 patients (59 per arm) were randomly assigned to receive IFN at a dose of 0.

Pilot trial of bone-targeted therapy with zoledronate, thalidomide, and interferon-gamma for metastatic renal cell carcinoma.

Background: The purpose of the study was to evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and interferon-gamma in patients with renal cell carcinoma and bone metastases.

Methods: Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment.