Efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
Ki Hyang Kim ◽  
Sun Young Rha ◽  
Ho Young Kim ◽  
Hye Ryun Kim ◽  
Jong-Mu Sun ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Ecog Performance Status

e15573 Background: We investigated the efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma (mRCC). Methods: From Korean Renal Cell Cancer Registry (KRCCR, http://kcsg-rcc.or.kr), we searched renal insufficiency patients with mRCC treated with sunitinib as a first-line treatment between January 2008 and May 2012. The Crockcroft-Gault formula was used for calculation of glomerular filtration rate and selected patients with chronic renal failure not requiring dialysis. Patients characteristics, clinical outcomes, toxicities were evaluated. The patients were divided by 2 groups based on the National Kidney Foundation definition of renal impairment and overall survival (OS) and progression-free survival (PFS) were obtained. Results: From total 997 enrolled from KRCCR, 34 patients were evaluated. Patients characteristics included: median age 66 years, ECOG performance status of 0 and 1 were 90%, and median GFR 46.5 ml/min/1.73m2 (range, 21.1-59.5). The starting dose of sunitinib was 50 mg for 22 patients and 37.5 mg for 12 patients. A schedule of sunitinib was 4 weeks on-2 weeks off for 31 patients, 2 weeks on-2 weeks off for 1 patient and daily for 2 patients. Best response was partial response (N=8) or stable disease (N=12). The median OS and PFS was 26.3 (95% CI: 17.1-35.3) and 12.2 (95% CI: 10.2-13.2) months, respectively. Log rank analysis revealed that severity of renal impairment was significantly associated with PFS but not with OS. Most common adverse events (AEs) of non-hematologic toxicities were stomatitis, rash, general edema and fatigue. The most common grade ≥3 AEs were fatigue, neutropenia and thrombocytopenia. Conclusions: Renal insufficiency patients with metastatic RCC did not impact on the efficacy of sunitinib and did not increased toxicities. Clinicians should not hesitate to treat renal insufficiency patients with metastatic renal cell carcinoma.

Nephrectomy Followed by Interferon Alfa-2b Compared With Interferon Alfa-2b Alone for Metastatic Renal Cell Cancer

2021 ◽  
pp. 113-118
Author(s):  
Christopher Weight
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Interferon Alfa ◽  
Cytoreductive Nephrectomy

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.

Current and Emerging Treatments for Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 18 (5) ◽  
pp. 468-479 ◽  
Author(s):  
Carla Cavaliere ◽  
Carmine D`Aniello ◽  
Chiara Della Pepa ◽  
Salvatore Pisconti ◽  
Massimiliano Berretta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Special Focus ◽  
Systemic Treatments

In the last decades, the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An additional knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progress, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival. To date, there are few data about the optimal sequential use of the TTs hence, in clinical practice, the therapeutic strategy is chosen on the basis of the safety profile of the drug, patients medical history and the pivotal trial results, though such studies often exclude patients with poor performance status and/or severe comorbidities that we routinely see in our clinics. This review aims to provide an overview of the systemic therapies for mRCC both in the newly diagnosed patients and in the subsequent lines of treatment, with a special focus on the last advances about TTs and immunotherapy.

Evaluation of parameters for treatment duration of sunitinib in metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15042-e15042
Author(s):  
Ellen Kossoff ◽  
Nicolas Batty ◽  
Alice C. Ceacareanu ◽  
Kristopher Attwood ◽  
Dustyn Miller ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Treatment Duration ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Lower Baseline

e15042 Background: In metastatic renal cell carcinoma (mRCC), there is a need for predictive indicators for treatment duration (TD) of sunitinib. Our study evaluates parameters that may be associated with TD of sunitinib. Methods: From 01/2007-12/2011, consecutive mRCC patients (pts) were reviewed. Responders (R) were defined as having either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, while non-responders (NR) were defined as having either stable disease (SD) or progressive disease (PD). Long term duration (LTD) was defined as therapy with sunitinib ≥ 18 months (mos). Hazard ratios (HR) and 95% confidence interval (95CI) representing the association between TD and specific parameters were computed with Cox proportional hazard model. Results: After a median follow-up of 9.8 mos (<1 - 63.8) of 128 mRCC pts, 57 (45%) received sunitinib. Responses were CR, PR, SD, PD of 3, 13, 8 and 33 pts, respectively. LTD was observed in 9 pts (21%). Hemoglobin < 12.5 g/dL (p = 0.048), prior nephrectomy (PN) (p = 0.001), prior therapies (p = 0.016), dose reduction (DR) (p = 0.001), an increased skin toxicity (p = 0.025) and low/intermediate (LI) Memorial Sloan-Kettering Cancer Center (MSKCC) risk-groups (p = 0.003) were associated with longer TD and a higher ANC (p < 0.0001) with shorter TD. In the multivariate analysis, PN was the only significant prognostic factor [HR 0.3 (95CI 0.12 -0.72) p = 0.007] that was associated with prolonged TD. Pts with LTD had a lower baseline ANC (p= 0.037), a LI MSKCC (p = 0.026), higher frequency of DR (p = 0.007), increased skin (p = 0.017) and endocrine (p = 0.015) toxicities and an increase of body mass index (BMI) from baseline (p = 0.008). When adjusted for BMI and performance status, results were maintained. Progression free survival (PFS) and overall survival (OS) of pts with LTD were not reached. However, both PFS and OS of R with TD < 18 mos, were 19.5 mos 95CI (3.4 - 27.9). Conclusions: PN, lower baseline ANC, DR, an increase of BMI from baseline, skin and endocrine toxicities were associated with prolonged TD of sunitinib in mRCC. There is a need for prospective studies to develop a predictive TD model in this setting.

Overall and progression-free survival with everolimus, temsirolimus, or sorafenib as second targeted therapies for metastatic renal cell carcinoma: A retrospective U.S. chart review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4612-4612 ◽  
Author(s):  
Hongbo Yang ◽  
Michael K.K. Wong ◽  
James E. Signorovitch ◽  
Xufang Wang ◽  
Zhimei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Chart Review ◽  
Performance Status ◽  
Progression Free Survival ◽  
Free Survival ◽  
Baseline Characteristics

4612 Background: Tyrosine kinase inhibitors (TKIs) (sorafenib, sunitinib, pazopanib) and inhibitors of the mammalian target of rapamycin (mTORs) (everolimus, temsirolimus) are used for treating metastatic renal cell carcinoma (mRCC) following initial treatment with a TKI. This study’s objective was to establish the effectiveness of the most commonly used 2nd line treatments based on real-use data. Methods: mRCC patients who received a TKI as their 1st targeted therapy and everolimus, temsirolimus or sorafenib as their 2nd therapy were identified by oncologists (85% in community practice) throughout the US as part of an online chart review study. Baseline characteristics were assessed prior to 2nd targeted therapy, including type and duration of initial TKI, response, histological subtype, performance status, and sites of metastasis. Overall survival (OS) and progression free-survival (PFS) were assessed after initiating 2nd targeted therapy. OS and PFS were compared between treatment groups using Cox proportional hazards models adjusted for baseline characteristics. Results: Charts were reviewed for 233, 178, and 123 mRCC patients receiving everolimus, temsirolimus, and sorafenib after an initial TKI, respectively. Median age was 64 years and 70.4% were male. Prior to initiating a 2nd targeted therapy, 86.0% used sunitinib and 85.9% had disease progression. After adjusting for baseline characteristics, everolimus was associated with significantly prolonged OS compared to temsirolimus (hazard ratio [HR] 0.56; CI 0.40-0.78; p<0.001) and sorafenib (HR 0.65; CI 0.42-0.99; p=0.047). Everolimus was associated with significantly longer PFS compared to temsirolimus (HR 0.73; CI 0.55-0.96; p=0.025), and non-statistically significant longer PFS compared to sorafenib (HR 0.75; CI 0.53-1.07; p=0.110). Results were similar in the subgroup with sunitinib as 1st targeted therapy and the subgroup with progression on 1st TKI. Conclusions: Among mRCC patients with prior TKI treatment, everolimus was associated with significantly prolonged OS and PFS compared to temsirolimus and significantly prolonged OS compared to sorafenib.

Phase II presurgical study of bevacizumab plus erlotinib in untreated patients with metastatic renal cell carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5004-5004
Author(s):  
E. Jonasch ◽  
D. Tsavachdidou ◽  
C. G. Wood ◽  
S. F. Matin ◽  
P. G. Corn ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Study Drug ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Free Survival

5004 Background: The safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC) is not known. The current study was designed to answer these clinical questions, and to define predictive tissue biomarkers using nephrectomy specimens from patients on trial. Methods: Patients with newly diagnosed clear cell mRCC whose primary tumor was considered resectable were enrolled. In this single arm phase II trial, patients received bevacizumab plus erlotinib or bevacizumab alone for 8 weeks, followed by restaging. Primary endpoint was progression free survival (PFS). If patients demonstrated progressive disease and had a declining performance status after eight weeks, nephrectomy was deferred. Postoperatively, patients continued on study drug(s) if disease stabilization or regression had occurred. Reverse phase protein arrays (RPPAs) were generated from nephrectomy specimens. Results: Between March 2005 and March 2008, 52 patients were enrolled on the study, and 50 were included in the analysis. By the Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk features. Twenty-three patients received bevacizumab plus erlotinib, and 27 received bevacizumab alone. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI: 5.5, 15.6 months). Median overall survival was 25.4 months (95% CI 11.4, not estimable). Two perioperative deaths occurred, and neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients. RPPA analysis demonstrated a clear separation of better versus worse responding patients. Conclusions: Presurgical treatment with bevacizumab therapy is relatively safe and yields clinical outcomes comparable to post surgical treatment with antivascular therapy in patients with mRCC. Prospective randomized trials testing the use of presurgical therapy to select appropriate patients for cytoreductive nephrectomy are warranted. [Table: see text]

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma

2021 ◽  
pp. 107815522110055
Author(s):  
Ruggero Lasala ◽  
Fiorenzo Santoleri ◽  
Alessia Romagnoli ◽  
Felice Musicco ◽  
Paolo Abrate ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Relevant Literature ◽  
Real Life ◽  
Ecog Performance Status ◽  
Target Therapies ◽  
Baseline Characteristics

Introduction Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. Materials and Methods Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. Results We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS. Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

scholarly journals Prognostic value of DCE-CT-derived blood volume and flow compared to core biopsy microvessel density in patients with metastatic renal cell carcinoma

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Aska Drljevic-Nielsen ◽  
Finn Rasmussen ◽  
Patricia Switten Nielsen ◽  
Christina Stilling ◽  
Kennet Thorup ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Blood Volume ◽  
Metastatic Renal Cell Carcinoma ◽  
Microvessel Density ◽  
Renal Cell ◽  
Core Biopsy ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Tumour Metastasis

Abstract Background Angiogenesis is prominent in metastatic renal cell carcinoma (mRCC). We compared two angiogenesis assessment methods: dynamic contrast-enhanced computed tomography (DCE-CT)-derived blood volume (BV) and blood flow (BF) and core biopsy microvessel density (MVD). Methods As planned in DaRenCa Study-1 study, DCE-CT and core biopsy were performed from the same tumour/metastasis at baseline. MVD was assessed by CD34 immunostaining in tumour (CD34-indexT) or tumour including necrosis (CD34-indexTN). BV and BF were assessed using the DCE-CT software. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier analysis. Spearman coefficient (rho) tested the correlation between MVD and BV, BF, or CT density (HU). Results At baseline, 25 patients had analysable scans and tissue. BVdeconv, BVPatlak, and BFdeconv > median were associated with favourable OS (43.2 versus 14.6 months, p = 0.002; 31.6 versus 20.2 months, p = 0.015; and 31.6 versus 24.5 months, p = 0.019). CD34-indexT and CD34-indexTN did not correlate with age (p = 0.543), sex (p = 0.225), treatment (p = 0.848), International mRCC Database Consortium category (p = 0.152), synchronous versus metachronous metastatic disease (p = 0.378), or tumour volume (p = 0.848). CD34-indexT or CD34-indexTN > median was not associated with PFS (p = 0.441 and p = 0.854, respectively) or OS (p = 0.987 and p =0.528, respectively). CD34-indexT or CD34-indexTN was not correlated with BV, BF, or HU (rho 0.20–0.26). Conclusions Differently from MVD, DCE-CT-derived BV and BF had prognostic impact and may better reflect angiogenesis in mRCC. Trial registration NCT01274273

scholarly journals Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study

2021 ◽  
Vol 28 (2) ◽  
pp. 1402-1411
Author(s):  
Koji Iinuma ◽  
Koji Kameyama ◽  
Kei Kawada ◽  
Shota Fujimoto ◽  
Kimiaki Takagi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Efficacy And Safety ◽  
Lymphocyte Ratio

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

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