Kidney Cancer

The US Food and Drug Administration (FDA) has approved everolimus (Afinitor) oral tablets for the treatment of patients with advanced kidney cancer whose disease has progressed after treatment with other cancer therapies. Everolimus is intended for patients with advanced renal cell cancer who have already tried another kinase inhibitor (sunitinib [Sutent] or sorafenib [Nexavar]).

A study of nearly 1,500 patients treated for kidney cancer at UCLA in the past 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.

The advisory committee tothe UK’s National Health Service(NHS) has recommended that theNHS not pay for four new agentsproven effective in metastatic renalcell carcinoma. The four drugs arebevacizumab (Avastin), sorafenib(Nexavar), sunitinib (Sutent), andtemsirolimus (Torisel).

Patients with advanced renal cell carcinoma (RCC) treated with single-agent, oral sunitinib malate (Sutent) reported experiencing significantly lower severity of symptoms like bone pain and breathlessness, among others, than patients treated with interferon-alfa.

The lead investigator in an evaluation of bevacizumab (Avastin) combined with sunitinib malate (Sutent) for renal cell carcinoma (RCC) said the project would be abandoned. FDA issued a product safety alert after Genentech, Avastin’s developer, reported serious complications in several patients enrolled in the phase I trial.

Radiation therapy (RT) and immunotherapy of cancer both date back more than 100 years, and yet, because radiation was often considered immunosuppressive, there had been little enthusiasm for combining them until recently. Immunotherapy has an established role in the treatment of some cancers-superficial bladder cancer treated with bacillus Calmette-Guérin (BCG), renal cell carcinoma and melanoma treated with interferon and interluekin (IL)-2 (Proleukin), and breast cancer and lymphoma treated with monoclonal antibodies such as trastuzumab (Herceptin) and rituximab (Rituxan), which partly function through antibody-dependent cellular cytotoxicity.

Wyeth Pharmaceuticals recently announced the initiation of the INTORACT (INvestigation of TORisel and Avastin Combination Therapy) study, a worldwide randomized, open-label, phase IIIB study comparing temsirolimus (Torisel) plus bevacizumab (Avastin) vs bevacizumab plus interferon-alfa for first-line treatment of patients with advanced renal cell carcinoma (RCC). Wyeth Research is conducting the INTORACT study with the support and assistance of Roche and Genentech

COLLEGEVILLE, Pennsylvania-Wyeth Pharmaceuticals has initiated the INTORACT (Investigation of Torisel and Avastin Combination Therapy) trial, a worldwide randomized open-label phase IIIb study comparing temsirolimus (Torisel) plus bevacizumab (Avastin) vs bevacizumab plus interferon-alfa for the first-line treatment of patients with advanced renal cell carcinoma.

A multicenter study has found that the experimental targeted therapy everolimus (Cetican, RAD001) delays cancer progression in patients with metastatic kidney cancer that has progressed despite treatment with other targeted therapies. Lead author Robert J. Motzer, md, attending physician at Memorial Sloan-­Kettering Cancer Center, presented the results at the ASCO meeting (abstract LBA5026).

CHICAGO-Everolimus prolongs progression-free survival in patients with metastatic renal cell carcinoma that has progressed despite treatment with inhibitors of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase, finds an international phase III trial (RECORD-1) presented at ASCO 2008 (abstract LBA-5026).

NEW YORK-Antigenics Inc.’s personalized cancer vaccine Oncophage (vitespen) has received its first government approval.

Epothilones, representing a newer class of naturally occurring antimicrotubule macrolides, have emerged as cytotoxic agents with significant antitumor activity against tumors that are resistant to taxanes.

Ms. Donovan and Dr. Vahdat present a review of the literature on a novel class of agents, the epothilones, focusing in particular on the two most-investigated agents to date-patupilone and ixabepilone (Ixempra).

The introduction of imatinib mesylate (Gleevec) has dramatically changed the management and prognostic outlook of patients with chronic myeloid leukemia (CML).

Drs. Rini and Bukowski do an excellent job of updating and commenting on the rapidly evolving field of therapy for metastatic renal cell carcinoma (RCC).

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).