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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).
Dr. Tim Eisen provided an update on the sorafenib (Nexavar) phase III trial in patients with advanced renal cell carcinoma (RCC), or kidney cancer, during the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. Dr. Eisen is the consultant medical oncologist at The Royal Marsden Hospital in London. The updated analysis confirmed that overall survival was longer for sorafenib than for placebo patients.
The introduction of newer classes of chemotherapeutic agents, with varying mechanisms of action by which they affect tumor growth and viability, has challenged the traditional norms of clinical trial design and drug approval in oncology. Most notably, the emergence of cytostatic biologic agents with antitumor efficacy has necessitated reassessment of appropriate primary endpoints for phase II and III trials in advanced disease from both a clinical and regulatory standpoint. Recent data in the field establishes an endpoint hierarchy, which places progression-free survival (PFS) between overall survival (OS) and response rate (RR) as appropriate primary endpoints for assessing the clinical efficacy of cytostatic and cytotoxic agents.
Although improved survival is the "gold standard" for proving clinical benefit of oncologic therapy, the US Food and Drug Administration (FDA) has accepted significant results in clinical trials using surrogate endpoints as the basis for drug approval. One surrogate is the amount of tumor reduction, or tumor response. Although tumor shrinkage would seem to be a necessary precondition for improved survival, clinical studies of a variety of oncologic agents have not consistently demonstrated a correlation between the two in patients with renal cell carcinoma. Moreover, tumor response may not be an appropriate endpoint for evaluating the effects of the new targeted therapies, whose putative mechanisms are generally cytostatic rather than cytotoxic. Clinical trials suggest that some patients with other solid tumors, such as lung cancer, may derive clinical benefit from treatment that helps stabilize their disease. There is also controversy as to whether the Response Evaluation Criteria in Solid Tumors (RECIST) provides the most appropriate instrument for assessing tumor burden. Ultimately, use of a variety of endpoints as well as different trial designs may provide an adequate basis for investigating the benefits/risks of newer therapies.
This report of a case of cytokine-refractory metastatic, clear-cell renal cell carcinoma (RCC) presents some current issues related to use of targeted therapy in the community. Due to the different mechanisms of cytostatic vs cytotoxic agents, traditional response assessments may not always apply in deciding when to either continue or stop treatment. While community physicians may increasingly focus more on duration of response, symptom relief, and how well patients tolerate treatment, there is a clear need for validated surrogate markers of biologic activity and response, as well as randomized trials that directly compare some of the targeted therapies being applied in advanced RCC.
The manuscripts that comprise this supplement "Defining Clinical Endpoints in Renal Cell Carcinoma" are presented by six leading international clinical and basic investigators, and are derived from their presentations at the roundtable discussion, "Defining Clinical Endpoints in Renal Cell Carcinoma," which took place in Chicago on October 21, 2005, sponsored by Bayer HealthCare.
Several novel targeted agents are being tested for the treatment of advanced renal cell carcinoma (RCC), and results of phase I and II trials have been encouraging. A recently completed phase III, placebo-controlled study showed that median progression-free survival doubled from 12 weeks to 24 weeks in patients treated with the multi-kinase inhibitor sorafenib (Nexavar) (hazard ratio [HR], 0.44; P < .00001), and approximately three-quarters of patients had some degree of tumor regression. Furthermore, interim analysis showed an estimated 39% improvement in overall survival in sorafenib-treated patients (HR, 0.72; P = .018) and an investigator-assessed response rate of 10%, indicating that many more patients had clinical benefit than had tumor regression qualifying as response by traditional criteria. These data and others have added to the evidence of lack of correlation between response rate and clinical benefit in RCC patients (as well as in other tumor types) treated with targeted therapies. Issues surrounding study endpoints and biologic efficacy markers for molecular targeted agents in RCC are discussed in this article, with a focus on results of the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGETs).
Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
The US Food and Drug Administration (FDA) recently approved sunitinib malate (Sutent) capsules for two types of cancer: advanced renal cell carcinoma and malignant gastrointestinal stromal tumor (GIST), after disease progression on or intolerance to the frontline drug imatinib mesylate (Gleevec).
For the first time, the US Food and Drug Administration (FDA) has granted a new oncologic drug product approval for indications for two different cancers simultaneously. The agency approved Sutent (suniti-nib, Pfizer) for the treatment of patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib (Gleevec) or who are unable to tolerate imatinib. It also granted Sutent accelerated approval for treating advanced renal cell carcinoma (RCC).
The Food and Drug Administration (FDA) has approved Nexavar (sorafenib tosylate) tablets for the treatment of patients with advanced renal cell carcinoma. Nexavar, a multikinase inhibitor that has been shown to double progression-free survival in these patients, is the first FDA-approved treatment for this type of cancer in more than a decade, Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc.
Although resection currently remains the standard of care for renalcarcinoma, the search for less invasive treatments has led to alternativesurgical approaches. Even less invasive, and appropriate for manygroups of patients, is percutaneous radiofrequency ablation, which inducestumor necrosis via lethal hyperthermia. Multiple series of renaltumors treated with percutaneous ablation in vivo and left in situ havebeen published; these series reveal that for small renal tumors,radiofrequency ablation results in complete necrosis at imaging in 79%to 100% of cases. Because current results come from tumors left in situwith short postablation follow-up, long-term results are necessary tocompare outcomes to surgical standards. Complication rates are lowerthan those following partial nephrectomy. Future reports will shed lighton the long-term outcomes of percutaneous ablation and the relativeadvantages and disadvantages of various technologies for thermal ablation.
This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.
This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.
ASCO - In a large randomized double-blind phase III international trial in patients with previously treated metastatic renal cell cancer (RCC), the oral multikinase inhibitor sorafenib (BAY 43-9006) was well tolerated and doubled progression-free survival (PFS) vs placebo with best supportive care. Lead investigator Bernard Escudier, MD, presented interim results in 769 patients at the 41st Annual Meeting of the American Society of Clinical Oncology (LBA4510) on behalf of the BAY 43-9006 TARGETs Clinical Trial Group. The primary endpoint of the study, overall survival, has not yet been reached, he said, and will be reported at a later date.
Renal-cell carcinoma (RCC) is curable only in patients presenting with resectable, early-stage disease. Advanced local or metastatic disease carries an approximate 15% 5-year survival rate. However, the natural history of metastatic RCC is heterogeneous, and aggressive palliative treatment is recommended, especially for patients with a solitary metastatic site and good performance status.
