Kidney Cancer

Temsirolimus (Torisel) improves overall survival in patients with clear-cell renal cell carcinoma (RCC) and other histologies, including papillary RCC, according to a study presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago. The exploratory analyses, reported in a poster presentation by Janice Dutcher, MD, and an international team of colleagues, suggest that temsirolimus benefits patients regardless of age or tumor histology, and may benefit those in both poor- and intermediate-risk groups.

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.

An updated analysis from the pivotal phase III trial of sunitinib (Sutent) in 750 previously untreated patients with metastatic renal cell cancer (RCC) has reaffirmed the superior efficacy of sunitinib, compared with interferon-alfa (IFN-a) and shown that the agent prolongs progression-free survival (PFS) across all patient groups

Prognostic factor models can provide important information to help patients and clinicians make treatment decisions. These decisions have become more complex in the selection of treatment for patients with metastatic renal cell carcinoma (RCC).

Integrins have direct effects in stimulating proliferation and preventing apoptosis in cancer cells and mediating proangiogenic interactions between endothelial cells and extracellular matrix. Alterations of expression of various integrins and their receptors have been observed in various cancers in which angiogenesis is known to play a role, including colorectal cancer. Inhibition of specific integrins might thus inhibit both direct effects of integrins on cancer cells and tumor angiogenesis. Inhibitory peptides and anti-integrin monoclonal antibodies are currently being investigated in clinical trials in patients with solid tumors, with early evidence suggesting clinical benefit in disease stabilization with use of an anti-αvβ3 antibody in the settings of colorectal cancer, renal cell carcinoma, and melanoma. Integrin inhibition alone and with other targeted therapeutic approaches should be further investigated in clinical trials in patients with colorectal cancer.

Torisel has become the third drug in 18 months to win FDA approval for the treatment of advanced renal cell carcinoma. Torisel (temsirolimus, Wyeth Pharmaceuticals) received its marketing approval on the basis of data from a phase III clinical trial showing increased survival with single-agent Torisel, compared with interferon-alfa, which was the standard at the time the study was designed.

FDA has approved Wyeth's Torisel (temsirolimus) for the treatment of advanced renal cell carcinoma, based on a study showing prolonged survival with Torisel as a single agent vs interferon alfa

Wyeth Pharmaceuticals recently announced that the US Food and Drug Administration (FDA) has approved temsirolimus (Torisel) for patients with advanced renal cell carcinoma (RCC).

This year's plenary presentations at the American Society of Clinical Oncology annual meeting, held in Chicago on June 1-5, addressed a variety of issues in five major cancer types.

Paralleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell cancer (RCC).

EntreMed has initiated a phase II trial of its drug candidate Panzem (2-methoxyestradiol) in patients with metastatic renal cell carcinoma who have failed treatment with or are progressing while being treated with sunitinib (Sutent).

In appropriately selected patients, cryoablation of renal cancers results in equal efficacy, shorter hospital stays for patients, and lower costs when performed percutaneously instead of laparoscopically

FDA officials have granted regular approval to Sutent (sunitinib malate, Pfizer) for the treatment of advanced renal cell carcinoma (RCC) patients who failed prior cytokine-based therapy, upgrading it from the accelerated approval granted in January 2006.

In its second annual "Clinical Cancer Advances" report, the American Society of Clinical Oncology (ASCO) selected six notable developments in clinical cancer research as most important in 2006.

Treating metastatic renal cell carcinoma (RCC) prior to surgery with Avastin (bevacizumab) and Tarceva (erlotinib) appears safe, effective, and may prolong patient survival, researchers reported at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (abstract 250). Although the two agents have been tested previously as postoperative treatment for the disease, the new data provide the first evidence that presurgical treatment with the drugs may improve patient outcomes.

An innovative cancer agent called PHA-739358, which inhibits one of the aurora proteins, has shown indications of potential benefit in 7 of 36 patients (19.4%) with advanced or metastatic solid tumors who participated in a phase I dosing and toxicity study, Dutch researchers reported at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

The elegant and thoughtful review of current management of renal cell carcinoma, by Feldman and Motzer,[1] indicates that there has been clear and defined progress in the management of this frustrating disease. Our limited understanding of the biology of the immune response in renal carcinoma has led to the use of the interferons and varying doses of interleukin-2 (Proleukin), occasionally and inconsistently achieving spectacular, durable responses, but often at the cost of significant toxicity.

Endocare, Inc, a medical device company focused on the development of minimally invasive technologies for tissue and tumor ablation, announced that six studies and papers demonstrating the effectiveness of cryoablation for treating renal cancer were published in a supplement to the July 2006 issue of Urology.

For the past 20 years, the systemic treatment of metastatic renal cell carcinoma (RCC) has been limited primarily to cytokines, with few patients showing benefit. However, recent advances in understanding the pathobiology of RCC have led to the identification of novel therapeutic targets for this disease. Drugs specifically designed to inhibit these targets have been developed, with several showing superior efficacy over traditional cytokine therapy. Moreover, these agents are well tolerated and have improved the span of progression-free, and in some cases, overall survival. As a result, between December 2005 and January 2006, two of these targeted therapies—sunitinib (Sutent) and sorafenib (Nexavar)—were approved by the US Food and Drug Administration for the treatment of advanced RCC. The authors review the clinical trials that have focused on these two drugs as well as those concentrating on two other promising agents, bevacizumab (Avastin) and temsirolimus. The ways in which these novel drugs are changing the standard of care for metastatic RCC and the future directions of RCC clinical trials are also discussed.

The science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.

Argos Therapeutics has begun a phase I/II clinical trial to test the activity and safety of AGS-003, a personalized immunotherapy for advanced kidney cancer. AGS-003 is a second-generation dendritic-cell-based therapy with optimized immune response characteristics designed to stimulate the immune system to target and destroy cancer cells.

The investigational agent lapatinib (Tykerb, GlaxoSmithKline) extended survival in the 61% of renal cell carcinoma (RCC) patients whose tumors overexpressed EGFR at the 3+ level

This case study illustrates some of the off-treatment issues your patients may face when their coping support system is inadequate. Some of the psychological effects cancer patients deal with do not manifest until years after treatment is completed.

A phase I trial is testing triple therapy targeted at both the epidermal growth factor receptor (EGFR) pathway and the vascular endothelial growth factor (VEGF) pathway in patients with solid malignancies.

Two phase III international randomized trials of sunitinib (Sutent) and of the investigational mTOR kinase inhibitor temsirolimus indicate targeted therapy may provide both clinical and survival benefits to patients with advanced renal cell carcinoma (RCC). Sunitinib is an oral multi-targeted receptor tyrosine kinase inhibitor of the VEGF and PDGF receptors.

Cryoablation of small renal tumors is associated with a 98% cancer-specific survival rate after 5 years

According to a new multicenter study, the drug sunitinib malate (Sutent) is more effective than the current standard cytokine treatment given as initial therapy for patients with metastatic renal cell carcinoma. The study was presented at the annual American Society of Clinical Oncology meeting in Atlanta.

Preliminary data from an interim analysis of an ongoing phase III clinical trial of investigational temsirolimus (CCI-779) for the treatment of advanced renal cell carcinoma showed that single-agent therapy with temsirolimus significantly increased overall survival as a first-line treatment of patients with advanced disease and poor-risk features compared to interferon-alpha, a treatment for advanced renal cell carcinoma. In the trial, patients who were treated with temsirolimus alone experienced a 3.6-month, or 49%, increase in median overall survival time compared with patients treated with interferon-alpha alone (10.9 vs 7.3 months, P = .0069).