scholarly journals Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
An Uche ◽  
Chad Sila ◽  
Tad Tanoura ◽  
James Yeh ◽  
Neil Bhowmick ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Heavily Pretreated ◽  
Treatment Paradigm ◽  
Endothelial Growth Factor

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

scholarly journals Evolving Treatment Paradigm in Metastatic Renal Cell Carcinoma

2017 ◽  
pp. 319-329
Author(s):  
David M. Gill ◽  
Neeraj Agarwal ◽  
Ulka Vaishampayan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Mtor Inhibitors ◽  
Treatment Paradigm

The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel–Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies. The U.S. Food and Drug Administration (FDA) has thus approved a total of nine targeted therapies since 2005, including VEGF tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, sorafenib, and lenvatinib), a monoclonal antibody targeting VEGF (bevacizumab), mTOR inhibitors (temsirolimus and everolimus), and a multityrosine kinase inhibitor (cabozantinib). Furthermore, the development of immune checkpoint inhibitors has again shifted the mRCC therapeutic landscape with the FDA’s approval of nivolumab. Herein, we discuss the unprecedented changes in the field of clear cell histology mRCC in both the first-line and salvage settings, and we also discuss future therapies and recommend a treatment paradigm on sequencing of these agents.

Everolimus (EVE) versus temsirolimus (TEM) after first-line treatment with VEGF TKI in patients with metastatic renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 460-460
Author(s):  
Shiven B. Patel ◽  
Neeraj Agarwal ◽  
JoAnn Hsu ◽  
Srinivas Kiran Tantravahi ◽  
David Gill ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Similar Efficacy ◽  
Oral Drug ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Endothelial Growth Factor

460 Background: Given the lack of affordability with an oral drug like EVE and/or preference in some patients (pts), TEM has been used after disease progression on a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, efficacy of TEM and EVE in this setting has not been evaluated in a randomized trial. Methods: Pts who were treated with a first VEGF TKI for metastatic renal cell carcinoma (mRCC) and then treated with either EVE or TEM upon progression were identified from two institutional databases. Survival estimates of progression free (PFS) and overall survival (OS) were assessed from initiation of second-line (2nd) treatment by Kaplan-Meier methodology. Results: 90 pts were eligible that received either EVE (n=59; 66%) or TEM (n=31; 34%) in 2nd setting. Pts and disease characteristics were similar in both groups. Median PFS was not different, but OS was significantly improved with EVE (Table). Conclusions: After progression on a 1st VEGFTKI, 2nd EVE and TEM have similar efficacy in terms of PFS, but OS was significantly higher with EVE. Data need further validation in a larger cohort. [Table: see text]

The Evolving Landscape of Metastatic Renal Cell Carcinoma

2012 ◽  
pp. 299-302 ◽  
Author(s):  
Daniel Y. C. Heng ◽  
Toni K. Choueiri
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Predictive Biomarkers ◽  
Vascular Endothelial ◽  
Treatment Paradigm ◽  
Endothelial Growth Factor

Overview: The treatment paradigm in metastatic renal cell carcinoma (mRCC) has evolved over the last 5 years. There are now seven approved targeted therapies against the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. The use of targeted therapy, sequences, combinations, and investigational compounds will be discussed. Prognostic and predictive tools are detailed, although much work must be done to find predictive biomarkers in an effort to individualize therapy for patients.

scholarly journals Cytoreductive Nephrectomy Following Immunotherapy-Base Treatment in Metastatic Renal Cell Carcinoma: A Case Series and Review of Current Literature

2021 ◽  
Vol 28 (3) ◽  
pp. 1921-1926
Author(s):  
Scott J. Dawsey ◽  
Steven C. Campbell ◽  
Moshe C. Ornstein
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Case Series ◽  
Complete Response ◽  
Response To Therapy ◽  
Cytoreductive Nephrectomy ◽  
Cell Renal Cell Carcinoma ◽  
Treatment Paradigm

The role and timing of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based regimens is unclear. However, the ability to achieve a complete response for metastatic renal cell carcinoma likely requires a nephrectomy at some point during treatment. Here we present a case series of three patients with metastatic clear-cell renal-cell carcinoma who received front-line immunotherapy-based treatment and subsequently underwent a cytoreductive nephrectomy. All three patients had a complete response to therapy and have subsequently remained off systemic therapy for a median of 531 days (range, 476–602). We also review the limited literature in this setting and highlight ongoing clinical trials. Although the role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based treatment is uncertain, a subset of patients will benefit from either an immediate or deferred cytoreductive nephrectomy. Ongoing trials are underway to further determine how to incorporate cytoreductive nephrectomy into the treatment paradigm for patients with metastatic renal cell carcinoma.

Correlation Between the Tyrozinkinazine Inhibitor Sunitinib - Dose, Schedule of Administration and Adverse Events

2017 ◽  
Vol 68 (7) ◽  
pp. 1652-1659
Author(s):  
Dana Lucia Stanculeanu ◽  
Raluca Ioana Mihaila ◽  
Daniela Zob ◽  
Oana Catalina Toma ◽  
Raluca Ioana Mihaila ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Dose Reduction ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Dose Schedule ◽  
Prophylactic Measures ◽  
Hand Foot Syndrome

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated survival benefit in patients with metastatic renal cell carcinoma (mRCC) and is generally well tolerated with most adverse events, manifesting as mild to moderate in severity. The most frequent related adverse events include hand-foot syndrome (HFS), hypertension, proteinuria, cardiac toxicities, myelosuppression, fatigue/asthenia, hypothyroidism, diarrhea and hepatotoxicity. The study aims to determine incidence of adverse events among patients with metastatic renal cell carcinoma (mRCC) treated Sunitinib within five years from 2010 to 2015 and comparing the results with data from literature. The study included a total of 56 patients treated with Sunitinib, with a dose of 50 mg (Schedule 4/2). Due to adverse events and individual safety and tolerability, at the indication of the personal clinician, 11 patients needed dose reduction, with a continuous dose of 37.5 mg, daily and 28 patients continued the dose of 50 mg taken daily, on a different schedule (2/1 schedule). The most important toxicities were anemia, leukopenia, thrombocytopenia, gastrointestinal effects (diarrhea), fatigue and hypertension. After dose reduction or modified schedule the incidence of the most frequent toxicities (HFS, leukopenia, thrombocytopenia and fatigue) decreased, but hypertension was still observed in 30% of patients. The results are similar with data from literature. Early identification of individuals at risk and monitoring patients during Sunitinib treatment is very important and it can facilitate early intervention with prophylactic measures or supportive treatment, thus increasing quality of life and adherence to treatment. Further studies need to establish which targeted population can benefit the most from adjusted regimens and to correlate them with prognostic factors for survival.

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