scholarly journals Role of Immunotherapy for Renal Cell Cancer in 2011

2011 ◽  
Vol 9 (9) ◽  
pp. 1011-1018 ◽  
Author(s):  
Saby George ◽  
Roberto Pili ◽  
Michael A. Carducci ◽  
Jenny J. Kim
Keyword(s):  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Current Status ◽  
High Dose

High-dose interleukin-2 (IL-2) and interferon were the most commonly administered therapies before the recent introduction of targeted agents, including vascular endothelial growth factor and mammalian target of rapamycin pathway inhibitors. Although the new agents result in a progression-free survival benefit, high-dose IL-2 remains the only agent with proven efficacy in producing durable complete and partial responses in patients with metastatic renal cell carcinoma (RCC). Furthermore, although the use of single-agent interferon has decreased significantly since the introduction of targeted therapy, it remains in the frontline setting in combination with bevacizumab as a result of 2 large phase III trials. Lastly, improved understanding of immune regulation has led to the advancement of targeted immunotherapy using immune checkpoint inhibitors that have shown promising activity and are moving forward in clinical development. This article focuses on the current status of immunotherapy in the management of metastatic RCC.

scholarly journals Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

2012 ◽  
Vol 1 (1) ◽  
Author(s):  
Sebastien Hotte ◽  
Tricia Waldron ◽  
Christina Canil ◽  
Eric Winquist
Keyword(s):  
Systematic Review ◽  
Renal Cell ◽  
Response Rate ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Mortality Data ◽  
High Dose ◽  
Eligibility Criteria ◽  
Free Survival

Objective: We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of interleukin-2 (IL-2) for the treatment of patientswith unresectable or metastatic renal cell carcinoma (RCC).Methods: We searched the literature to identify RCTs or meta-analyses of RCTscomparing treatment regimens with IL-2 to those without. Outcomes of interestincluded overall or progression-free survival, response rate, toxicity andquality of life.Results: We identified 36 RCTs, and 6 met the eligibility criteria (1098 patients).We studied IL-2 alone and in combination with other agents, including interferon-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamoxifen.No trials comparing high-dose IL-2 to non-IL-2 regimens were identified.A meta-analysis of 1-year mortality data from the 6 trials did not show a differencebetween IL-2-based regimens and non-IL-2 controls. Two of the 6trials detected statistically significant longer survival with IL-2 combinedwith IFN-a and 5-FU. Of the 4 trials that assessed progression-free survival, 3 reported significantly longer progression-free intervals with IL-2-based regimens.Five trials reported response rates; pooling the rates from these trialsgave an overall weighted response rate of 13.3% (range 9%–39%) and 5.3%(range 0%–20%) for IL-2-containing regimens and non-IL-2 regimens, respectively.IL-2-based regimens were more toxic than were non-IL-2 controls;the most frequently reported grade 3–4 toxicities were hypotension (range6%–68%), fever (2%–56%), nausea or vomiting or both (6%–34%), diarrhea(1%–28%) and cardiac toxicity (11%–25%). None of the trials reported healthrelatedquality-of-life data.Conclusion: Non-high-dose IL-2 containing regimens do not provide superiortreatment efficacy over non-IL-2-based regimens, with added toxicity, and thereforeshould not be used as standard treatment for patients with unresectableor metastatic RCC. High-dose IL-2 should only be used by experienced physiciansin the context of a clinical trial or investigative setting.

Dacarbazine, Cisplatin, and Interferon-Alfa-2b With or Without Interleukin-2 in Metastatic Melanoma: A Randomized Phase III Trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group

2005 ◽  
Vol 23 (27) ◽  
pp. 6747-6755 ◽  
Author(s):  
Ulrich Keilholz ◽  
Cornelis J.A. Punt ◽  
Martin Gore ◽  
Wim Kruit ◽  
Poulam Patel ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Single Agent ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Significant Difference ◽  
To Receive

Background Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma. Patients and Methods Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 × 106 U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 × 106 U/m2/6 hours, 18 × 106 U/m2/12 hours, 18 × 106 U/m2/24 hours, and 4.5 × 106 U/m2 for 3 × 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles. Results Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%). Conclusion Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

Should High-Dose Interleukin-2 Still be the Preferred Treatment for Patients with Metastatic Renal Cell Cancer?

2011 ◽  
Vol 26 (3) ◽  
pp. 273-277 ◽  
Author(s):  
Robert O. Dillman ◽  
Neil M. Barth ◽  
Louis A. VanderMolen ◽  
Warren H. Fong ◽  
Khosrow K. Mahdavi ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
High Dose ◽  
Metastatic Renal Cell Cancer

scholarly journals Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3750
Author(s):  
Yasir Khan ◽  
Timothy D. Slattery ◽  
Lisa M. Pickering
Keyword(s):  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Therapeutic Options ◽  
Current Status ◽  
Vegf Receptor ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.

Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma

2012 ◽  
Vol 08 (01) ◽  
pp. 30
Author(s):  
Mayer Fishman ◽  
Thomas Hutson ◽  
Neeraj Agarwal ◽  
Eric Jonasch ◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose

In recent years, the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of targeted therapies. Multitargeted kinase inhibitors (such as sunitinib, sorafenib, pazopanib, and axitinib), the vascular endothelial growth factor inhibitor bevacizumab, and mammalian target of rapamycin inhibitors (such as everolimus and temsirolimus) have become the standard of care for the palliation of metastatic disease. Unfortunately, cumulative toxicities and the lack of marked benefits have prevented the combined use of most molecularly targeted agents. Selected patients with mRCC benefit from immunotherapy, as subsets of patients can experience long-term disease remission or complete response with high-dose interleukin-2. In order to optimize the value of immunotherapy, improvements in the selection of drugs and combinations with novel immunomodulatory agents must be pursued.

High-dose bolus interleukin-2 in elderly patients (>60 years old) with metastatic melanoma or renal cell cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19559-19559
Author(s):  
J. Homsi ◽  
L. C. Kim ◽  
D. Goetz ◽  
D. Chen ◽  
M. Fishman ◽  
...  
Keyword(s):  
Side Effects ◽  
Metastatic Melanoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
The Elderly ◽  
Median Number ◽  
High Dose ◽  
Number Of Patients

19559 Background: Although durable complete responses have been reported from using high-dose bolus interleukin-2 (HDB IL-2) in a small number of patients with metastatic melanoma and renal cell cancer (RCC), IL-2 toxicity limits its use especially in the elderly. Methods: the medical records of patients older than 60 years old with melanoma or renal cell carcinoma who received HDB IL-2 at the Moffitt Cancer Center between 2000–2005 were reviewed. The effect of increased age, primary diagnosis, and the HDB IL-2 regimen used on the side effects, number of administered doses, and survival was analyzed. Results: 55 cycles were administered to 35 patients (23 RCC, 12 melanoma, 26 men). Median age was 67 years old (range: 61–77). 17 patients received a traditional regimen (one cycle: 600,000 IU/Kg intravenously every 8 hours for 14 doses repeated in 2 weeks, maximum of 28 doses) and 18 received a clinical trial regimen (one cycle: 600,000 IU/Kg intravenously every 8 hours for 5 doses repeated weekly, maximum of 20 doses). Median number of administered cycles was 1 (range 1–4) and median number of total doses was 24 (range 3–79). Increased age was not related to total number of administered doses. Median percentage of IL-2 administered in a cycle was 75% of planned (range 11%-100%). Reasons to discontinue therapy were: oliguria (35%), hypotension (25%), and arrhythmia (15%). Side effects in all cycles were: hypotension (71%), oliguria (67%), Arrhythmia (18%), Myocardial infarction (7%), pulmonary edema (7%), hypothyroidism (4%), confusion (4%), seizures (2%) and stroke (2%). Pressors were used in 58% of all cycles. 20 patients died within a year from starting treatment and 5 lived more than 2 years (4 had RCC). Conclusions: 1) HDB IL-2 has multiple and life-threatening side effects in the elderly and caution is needed when selecting these patients to such therapy 2) the number of doses administered is comparable to that general population 3) more studies are needed to identify the population that would mostly benefit from HDB IL2. [Table: see text] No significant financial relationships to disclose.

Effect of obesity on response to checkpoint inhibitors in renal cell cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 634-634
Author(s):  
Lakshminarayanan Nandagopal ◽  
Yousef Zakharia ◽  
Hesham Yasin ◽  
Kenneth Gerard Nepple ◽  
Mollie R. De Shazo ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
University Of Iowa ◽  
Obesity Status ◽  
Cox Proportional Hazard Regression ◽  
Definition Of

634 Background: Response to checkpoint inhibitors (CPIs) for renal cell cancer (RCC) remains variable, with markers like PDL1 proving unreliable. Preclinical models suggest that obesity could affect CPI outcomes. We conducted a retrospective study on the effect of obesity on outcomes in RCC patients treated with CPIs. Methods: RCC patients treated with nivolumab +/- Ipilimumab at university of Alabama at Birmingham (UAB) and University of Iowa (UIOWA) from 2015 - 2018 were classified according to WHO standard definition of BMI as non-obese (NOB-<30kg/m2) or obese (OB->30Kg/m2). Overall survival (OS) was defined as the interval from the first CPI dose to date of death or to last follow up date if patients were still alive. Progression free survival (PFS) was defined as the interval from the first dose of CPI to date of progression or date of death and censored at last follow-up date if patients were still alive without progression. Multivariable Cox proportional hazard regression model was used to evaluate the association between OS/PFS and obesity status, controlling for age, sex, race and number of prior therapies. All analyses were performed using SAS 9.4. Results: 84 patients with at least 6 months follow-up received a median of 9 doses of CPI with median follow of 72 weeks. 48 patients were NOB while 36 patients were OB, with 40 patients deceased at time of analysis. The most common response was stable disease in 45%, with CR in 5% and PR in 10% for a disease control rate of 63%. The median OS was 30 months in NOB patients and 20 months in the OB group. The 2 yr survival was 59% in the NOB group vs 28 % in the OB group with a HR of 0.60 (0.32-1.14; p=0.12). Median PFS was 13 months in the NOB group vs 7.3 months in the OB group with 2 yr PFS of 28% in the NOB group vs 5.5% in the OB group (HR 0.58 {0.35-0.98}; p=0.04). Conclusions: In this analysis of RCC patients treated with CPI, BMI < 30 predicts better OS and PFS. Further studies are required to better understand the effect of BMI on CPI outcomes in RCC.[Table: see text]

scholarly journals Predictors of Response to Targeted Therapy in Renal Cell Carcinoma

2012 ◽  
Vol 136 (5) ◽  
pp. 490-495 ◽  
Author(s):  
Laurie J. Eisengart ◽  
Gary R. MacVicar ◽  
Ximing J. Yang
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
High Dose ◽  
Predictors Of Response ◽  
Personalized Approach

Context.—The prognosis for patients with metastatic renal cell carcinoma is poor, with an average 5-year survival of approximately 10%. Use of traditional cytokine therapy, specifically high-dose interleukin 2, is limited by significant toxicity. Better understanding of the molecular pathogenesis of renal cell carcinoma has led to the development of targeted therapies to inhibit specific cellular pathways leading to tumorigenesis. These drugs provide improved survival with a more favorable toxicity profile. There is ongoing investigation of markers that predict response of an individual patient to different targeted therapies. Objective.—To explain the molecular basis for vascular endothelial growth factor inhibitor (antiangiogenic) and mammalian target of rapamycin inhibitor therapies for renal cell carcinoma, summarize the clinical trials demonstrating the effectiveness of these drugs, and describe the biomarkers shown to correlate with outcome in patients treated with targeted therapy. Data Sources.—All included sources are from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusion.—Emerging evidence shows promise that biomarkers will be useful for predicting an individual patient's response to targeted therapy, leading to a more personalized approach to treating renal cell carcinoma.

Sign in / Sign up

Export Citation Format

Share Document