Archive for September, 2008

Update on Metastatic Renal Cell Carcinoma

September 17, 2008

There have been three new drugs approved by the FDA for treatment of renal cancer between 2005 and 2007: Sorafenib (Nexavar), Sunitinib (Sutent), and Temsirolimus (Torisel).  These new drugs improve survival compared to best supportive care or older therapies, such as interferon-alpha.  The durgs have predictable and manageable toxicities, making them applicable to a broader array of patients than older therapies such as IL-2 (Interleukin-2/Proleukin) and interferon. 

High-dose IL-2 therapy remains an approved option for treatment.  It can produce complete and durable remissions in a minority of patients, but it requires administration in a specialized inpatient center with sophisticated monitoring by experienced physicians, because of the potential for serious, and even life-threatening toxicities.  This therapy is not suitable for patients with comorbid medical conditions, in most instances.  Therefore, for the majority of patients, treatment with newer agents is more likely to produce beneficial responses with lower overall toxicity risks.   That is the basis for the current standard-of-care, which is single-agent treatment with one of these newer drug choices.  Although combinations of newer therapies is under investigation, combination regimens are not apporved, and should not be used outside of clinical trials, because toxicity and risks of the various combinations is not well-defined, so safety is uncertain.  For example, a trial of the combination of an anti-VEGF (anti-vascular endothelial growth factor) antibody (becacizumab/Avastin) with Sunitinib was halted because of occurrence of a thrombotic microangiopathic hemolytic anemia in several patients. 

Sorafenib (Nexavar) was approved based on a second-line therapy trial that compared the drug to best supportive care in a cross-over design, which allowed patients who initially received placebo therapy to receive sorafenib at the time of progression.  The PFS (progression free survival) was 24 weeks for the sorafenib group versus 12 weeks for the placebo group.

Sunitinib (Sutent) was compared to INF (interferon-alpha) for first-line treatment.  The median PFS for the sunitinib group was 11 months, versus 5.1 months for the IFN group.  Updated survival analysis of the two groups did not reach a statistical difference between the two groups, but the survival was 27 months, marking a major change from the historical expectations for IFN-treated patients.

Temsirolimus (Torisel) was studied in the first-line setting versus IFN, or the combination of IFN + temsirolimus in patients with expected poor prognosis (as defined by the MSKCC criteria).  Therefore, the expectations of survival were much different than those in the Sutent study.  The median overall survival (OS) for the temsirolimus patients was 10.9 months, versus 7.4 months for IFN patients.

Selecting patients for these therapies then depends on a number of factors, such as disease burden, comorbid illness, overall performance status, prognostic factors (as predicted by the MSKCC prognostic model), oral versus intravenous therapy, and expected toxicity profiles of the drugs.  While Sutent therapy has become a common first-line drug selection, for most patients who are not going to receive high dose IL-2, they will be receiving a sequence of drug therapy, for example, beginning with Sutent therapy, and then moving ahead with one of the other drug selections at the time of treatment failure.   Therefore, it is not unreasonable for a patient to receive an alternative initial drug selection, for example temsirolimus, when the patient has high-risk MSKCC criteria, or non-clear cell histology.  In addition, patients may be entered into clinical trials of other new agents, or trials of drug combination therapy, reserving the approved therapies for consideration at the time of disease progression, if they are not part of the combination under study.

One such interesting clinical trial if the Argos AGS-003 Study, which tests sunitinib therapy in combination with a new immunotherapy product, autologous dendritic cells transfected with patient-specific tumor RNA.  This study is now active at CORT.  The IRB-approved patient brochure is attached, for further information on this study.  For more information, contact one of our Research Coordinators at 972-566-5588, or visit the CORT website at www.CORTPA.com.  Specific criteria must be met for entry into this study.  For patients who are not eligible, we offer other research and standard therapy options for management of their disease.

argos-patient-brochure_wirb-approved_15sep081

Although this brief summary has focused on management of patients with metastatic disease, these new agents are also being tested in patients with earlier stage disease who have not yet demonstrated metastases, i.e., in the adjuvant therapy setting.  CORT is participating in the ECOG 2805 Study of adjuvant sunitinib, sorafenib, or placebo.

Adjuvant Immunotherapy Study for Stage III Melanoma Open at CORT

September 13, 2008

CORT has opened a study of adjuvant non-interferon-based immunotherapy for patients with lymph-node positive cutaneous melanoma.  The study is enrolling patients who have had curative surgery and lymphadenectomy.  Patients who meet other clinical and lab eligibility criteria are potentially eligible.  This is a multicenter, multinational Phase III study of an anti-CTLA-4 therapy versus placebo for adjuvant therapy.   For further information about the study, contact one of our Study Coordinators at: 972-566-5588, or visit our website at www.CORTPA.com.