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Renal cell carcinoma (RCC) has been considered one of the most difficult tumors to treat for about 20 years. Chemotherapy and radiotherapy have almost no efficacy in this tumor, and cytokines (interleukin [IL]-2 [Proleukin] and interferon) have remained the only available treatment for about 20 years, with a small proportion of patients benefiting from these treatments.
Recent advances in the understanding of the biology of renal cell carcinoma (RCC) have been translated into clinical treatment options in metastatic disease.
An independent data monitoring committee stopped a phase III clinical trial of the investigational mTOR inhibitor everolimus (RAD001) after interim results showed significantly better progression-free survival in patients with advanced kidney cancer who received the drug, compared with placebo.
Sunitinib malate (Sutent, SU011248) is an oral multitargeted tyrosine kinase inhibitor used for treatment of renal cell carcinoma and gastrointestinal stromal tumor. We report a case of a patient who developed Guillain-Barré syndrome after initial treatment with sunitinib, with recurrent symptoms upon reintroducing the drug. This is the first report of such an effect. The literature on chemotherapy-induced Guillain-Barré syndrome is also reviewed. Oncology providers should be aware of this rare but potentially serious possible adverse effect of sunitinib.
Sunitinib (Sutent) is a cost-effective treatment for metastatic renal cell cancer, according to a report at the 14th European Cancer Conference
10 notable developments and events in cancer research and care
A growing number of novel antiangiogenic agents are entering clinical trials to study their clinical safety and efficacy. A few, such as bevacizumab (Avastin), sorafenib (Nexavar), and sunitinib (Sutent), have received US Food and Drug Administration approval and are already in widespread clinical use. As knowledge about the intricacies of intracellular signaling within multiple tumor types expands, agents with the capacity to impact these pathways are being incorporated into additional clinical trials alone and in combination with other targeted and/or traditional antineoplastic agents. Early clinical trials have focused on highly vascular tumor types, as well as those known to significantly overexpress the VEGF (vascular endothelial growth factor) receptor family. This article aims to review the status of antiangiogenic therapy in selected tumor types and discuss areas for further research.
The patient is a 39-year-old Caucasian male who presented with a right renal mass and painless gross hematuria. He underwent a right laparoscopic radical nephrectomy and the final pathology revealed a carcinoid tumor.
Preliminary phase I trial data suggest that the combination of recombinant IL-21 and sorafenib (Nexavar) is well tolerated in patients with metastatic renal cell carcinoma and has promising anti-tumor activity, lead investigator John A. Thompson, MD, and his colleagues reported
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.
