Proleukin (Interleukin-2) Therapy for Renal Cell Carcinoma: Treatment Option for Select Patients

Therapy options for patients with metastatic renal cell carcinoma has expanded significantly, with the FDA approval of sunitinib (Sutent), sorafenib (Nexavar), everolimus (Affinitor), temsirolimus (Torisel), and bevacizumab (Avastin).  These drugs have significant anti-tumor and anti-angiogenic effects.  Progression-free survival (PFS) is improved when compared to placebo or alpha-interferon (Intron-A) therapy.  Many patients will respond to more than one of these agents, and therefore overall outcomes for patients receiving sequential treatments may be improved.   These therapies have expected and manageable toxicities and risks, and are delivered on an outpatient basis.  Nonetheless, these new therapies do not offer curative potential to any patient when used in patients with established metastatic disease.   Patients with reduced overall health and function (performance status) can be treated with these agents.

Interleukin-2 (IL-2, Proleukin) is an FDA approved therapy for metastatic renal cancer.   It is a potent immune stimulator, and it may have anti-angiogenic activity.  Since its clinical development nearly two decades ago, it remains the only therapy with a known curative potential for patients with metastatic renal carcinoma.  Treatment with IL-2 has substantial toxicity, priniciply secondary to capillary leak syndrome and vasodilation, which can result in serious hypotension, fluid accumulation, edema, pulmonary congestion, renal dysfunction, or other organ failure.  Patient selection for this form of therapy is critical.  Only patients with good performance status and adequate kidney, heart, and lung function are potential candidates for IL-2 treatment.  Treatment is delivered on an inpatient basis, under carefully-monitored circumstances, usually in the intensive care unit.  Treatment is delivered by a specialized team of oncologists and nurses, who are familiar with the specific program of IL-2 therapy, and have experience in management and prevention of toxicities.   A critical care physician (ICU physician) is also engaged in management.  Therapy lasts for 5 days, with several additional days potentially required for resolution of treatment-related lab or clinical changes.  Most of the treatment-related side effects abate rapidly after the therapy is completed.  A second cycle of inpatient IL-2 therapy is given after the patient has had a brief period of outpatient recovery.   In studies of IL-2 in metastatic kidney cancer, the overall response rate (out of 255 patients) = 15% (7% complete, 8% partial). That is not higher than other recently-approved medications.  However, the median duration of complete response (CR*) is 6.7+ years (range 7 months – 10+ years).  Those long-term results are not achieved by other treatments for metastatic renal cancer.

Additional information about IL-2 therapy is available at www.Proleukin.com.  CORT is a provider for IL-2 therapy in the North Texas area.  Our patients are treated in Medical City Dallas Hospital.

For information about CORT, or to schedule a consultation about treatment of renal cancer, call 972-566-5588 to speak with a Patient Care Coordinator.  Additional information about CORT and directions are available at www.CORTPA.com.

Update on Metastatic Renal Cell Carcinoma

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.

Sunitinib (Sutent) for Metastatic Renal (Kidney) Cancer

Recent studies of sunitinib (Sutent) in patients with metastatic renal cell carcinoma have demonstrated it is effective in prolonging disease control and survival. The FDA-approved dosing regimen for Sutent is 50 mg per day orally for four weeks, followed by a 2-week rest period off of medication (the 4/2 regimen). CORT is conducting a study comparing a continuous dosing regimen of Sutent (37.5 mg per day orally, without treatment interruption) compared to standard dosing with the 4/2 regimen. The study will determine which regimen has superior outcomes and which has the least toxicity (side effects).

The risks of treatment on this study are fatigue, anemia, nausea, vomiting, diarrhea, proteinuria (protein in the urine), delayed wound healing, bleeding, or thrombosis.

For more information on our research studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

Post-Operative (Adjuvant) Therapy for Completely Resected Renal (Kidney) Cancer

After complete surgical resection of localized renal cell carcinoma, there is no existing standard post-operative therapy that is known to prevent or delay the occurrence of metastatic disease. Recent studies of sunitinib (Sutent) and sorafenib (Nexavar) in patients with metastatic renal cell carcinoma have demonstrated that both drugs are effective in prolonging disease control and survival. Based on these encouraging results, CORT is participating in the national study (ECOG 2805) for adjuvant treatment of resected, non-metastatic renal cell carcinoma. Patients who have complete resection of their renal tumors are eligible. Patients will be randomly assigned to either placebo therapy, treatment with Sutent, or treatment with Nexavar. Duration of treatment is approximately one year. Both drugs are orally administered. 

The risks of treatment on this study are fatigue, anemia, nausea, vomiting, diarrhea, proteinuria (protein in the urine), delayed wound healing, bleeding, or thrombosis.

For more information on our research studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.