Interferon Alfa-2b Three Times Daily and Thalidomide in the Treatment of Metastatic Renal Cell Carcinoma

2003 ◽  
Vol 21 (20) ◽  
pp. 3770-3776 ◽  
Author(s):  
Micaela Hernberg ◽  
Pekka Virkkunen ◽  
Petri Bono ◽  
Henna Ahtinen ◽  
Hanna Mäenpää ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Phase Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antiangiogenic Effect ◽  
Intention To Treat ◽  
Endothelial Growth Factor

Purpose: The antiangiogenic effect of interferon (IFN) may improve with frequent dosing and by combination with other agents with antiangiogenic activity. To evaluate this potential, we treated patients with metastatic renal cell carcinoma (RCC) with frequently dosed IFN and thalidomide. Patients and Methods: Thirty patients were given IFN-α-2b 0.9 MU subcutaneously three times daily for 1 month and subsequently 1.2 MU tid unless serious toxicity was encountered. Thalidomide was first given 100 mg/d for 1 week and 300 mg/d thereafter. Sera were collected before and during treatment for serum vascular endothelial growth factor (S-VEGF) analyses performed using enzyme-linked immunosorbent assay. Results: The intention-to-treat response rate was 20% (95% CI, 6% to 34%) and response rate for assessable patients (n = 27) was 22% (95% CI, 6% to 38%). All responses were partial. In addition, 17 patients (63%; 95% CI, 45% to 81%) had stable disease for 3 months or longer. The median time to treatment failure was 7.7 months, and median survival time was 14.9 months. The most common cause of thalidomide discontinuation was neuropathy. S-VEGF levels decreased more in patients who responded to therapy compared with those in patients whose condition had stabilized or who had progressive disease (P = .036). Conclusion: The combination of frequently dosed IFN-α-2b and low-dose thalidomide is feasible and active in advanced RCC, but the clinical benefit may remain small compared with that of IFN alone. Results from an ongoing phase III trial comparing IFN-α with or without thalidomide need to be analyzed before this combination can be recommended for use outside clinical studies.

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.

Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 293-293
Author(s):  
Florence Marteau ◽  
Brooke Harrow ◽  
Christine McCarthy ◽  
Joel Wallace ◽  
Alisha Monnette ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
P Value ◽  
The Real ◽  
The Us

293 Background: Checkpoint inhibitors (CPIs) are a treatment option for patients with metastatic renal cell carcinoma (mRCC), but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple receptor kinases implicated in tumorigenesis. In the US, cabozantinib is approved for use in patients with advanced RCC including after CPI treatment. Methods: This retrospective observational cohort study (NCT04353765) evaluated outcomes associated with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment. Eligible patients initiated TKI therapy between May 1, 2016 and Sep 31, 2019 and had received a CPI as their last systemic treatment prior to TKI therapy. Patients were identified from the US Oncology Network iKnowMed electronic health record database through structured queries and a targeted chart review. The following real-world outcomes were assessed: 6-month response rate (RR6months; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR6months was used to test for non-inferiority. Results: Eligible patients ( n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% ( n = 187) received cabozantinib and 24.3% ( n = 60) received other TKIs. All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%). Outcomes data are shown in the Table. Compared with other TKIs, cabozantinib was associated with a significantly higher RR6months and ORR, and TTD was twice as long with cabozantinib. Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment. AEs leading to discontinuation were consistent with the known safety profile of the products. Conclusions: In this mRCC population receiving routine care in the US, cabozantinib was used more frequently than other TKIs after CPI treatment. Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.abozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs. [Table: see text]

scholarly journals Impaired Retinal Circulation during Axitinib Treatment for Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 10 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Masashi Kimura ◽  
Sentaro Kusuhara ◽  
Mizuki Tagami ◽  
Makoto Nakamura
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Sudden Onset ◽  
Fundus Photography ◽  
Retinal Circulation ◽  
Circulatory Disorder ◽  
The Right ◽  
Endothelial Growth Factor

Purpose: Axitinib, an orally administered vascular endothelial growth factor receptors 1, 2, and 3 inhibitor, is widely used as the second-line treatment for metastatic renal cell carcinoma. We present a case of metastatic renal cell carcinoma who developed a novel ocular adverse event, impaired retinal circulation, during axitinib therapy. Methods: This is an observational case report. Results: A 57-year-old male who had been treated with axitinib for metastatic renal cell carcinoma for 2 years presented in August 2015. He complained of sudden-onset abnormal visual field in his right eye. His right eye exhibited multiple soft exudates on fundus photography and a significant fluorescein filling delay of the retinal vessels on fluorescein angiography. His best corrected visual acuity (BCVA) was 20/20 in the right eye, and a cecocentral scotoma was detected by Goldmann perimeter. As axitinib could have been responsible for impaired retinal circulation, axitinib was terminated and switched to temsirolimus. The soft exudates gradually subsided and the patients’ symptoms got better, but his right BCVA dropped to 20/63 3 months after the end of axitinib treatment with worsening of his general condition. Conclusion: Clinicians should be aware of retinal circulatory disorder that can occur in patients under axitinib treatment.

scholarly journals PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hannah L. Buckley ◽  
Fiona J. Collinson ◽  
Gemma Ainsworth ◽  
Heather Poad ◽  
Louise Flanagan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

Abstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing.

scholarly journals Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206

2010 ◽  
Vol 28 (13) ◽  
pp. 2137-2143 ◽  
Author(s):  
Brian I. Rini ◽  
Susan Halabi ◽  
Jonathan E. Rosenberg ◽  
Walter M. Stadler ◽  
Daniel A. Vaena ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-α) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-α versus IFN-α monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-α (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-α monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. Results Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-α and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-α monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-α. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-α. Patients who developed HTN on bevacizumab plus IFN-α had a significantly improved PFS and OS versus patients without HTN. Conclusion OS favored the bevacizumab plus IFN-α arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-α.

Patient-reported outcomes in a randomized trial of everolimus with metastatic renal cell carcinoma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17516-e17516
Author(s):  
J. Beaumont ◽  
D. Cella ◽  
T. Hutson ◽  
S. Bracarda ◽  
V. Grünwald ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Patient Reported ◽  
Secondary Analyses

e17516 Background: Patient-reported outcomes (PRO), including health-related quality of life (HRQL), were assessed in a Phase III trial of everolimus in metastatic renal cell carcinoma (mRCC) patients. Methods: Patients with mRCC were randomized (n=416) to receive everolimus or placebo plus best supportive care. Patients completed the FACT-Kidney Symptom Index- Disease Related Symptoms (FKSI-DRS) and EORTC-QLQ C30 at baseline and monthly during treatment. Karnofsky Performance Status (KPS) was also assessed at baseline and monthly during treatment. Primary analyses included time to deterioration defined as a decrease from baseline of at least 3 points for FKSI-DRS, at least 10% for EORTC Physical Function (PF) and Global Quality of Life (QL) scales, and at least 10 points for KPS. Secondary analyses considered tumor progressions that occurred prior to deterioration or censoring date as FKSI deterioration events and compared time to PRO deterioration by tumor progression. Comparisons were made using stratified log-rank tests and Cox proportional hazard models. Results: Time to deterioration in KPS was longer in the everolimus arm, and time to deterioration in FKSI-DRS was slightly longer ( Table ). There was no difference in time to deterioration in PF or QL. Secondary analyses showed median time to deterioration in FKSI-DRS was approximately doubled for the everolimus arm compared to placebo, and patients who progressed experienced a more rapid deterioration in FKSI-DRS and QL scores. Conclusions: Compared to placebo everolimus delayed progression of disease-related symptoms and KPS. No effect on time to deterioration of PF or QL could be determined. Secondary analyses suggest a delay in deterioration in kidney cancer related symptoms via tumor control. [Table: see text] [Table: see text]

TARIBO trial: Cytoreductive nephrectomy in metastatic renal cell carcinoma patients treated with targeted agents.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4601-TPS4601
Author(s):  
Paolo Grassi ◽  
Elena Verzoni ◽  
Alessandra Bearz ◽  
Sergio Bracarda ◽  
Marco Bregni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Clinical Benefit ◽  
Renal Cell ◽  
Primary Objective ◽  
Phase Iii ◽  
Rank Test ◽  
Cytoreductive Nephrectomy ◽  
To Receive

TPS4601 Background: In the cytokine era cytoreductive nephrectomy (CN) has been shown to increase survival in patients (pts) with metastatic renal cell carcinoma (mRCC). Efficacy of tyrosine kinase inhibitors (TKIs), including first-line sunitinib and pazopanib has been demonstrated. It is unclear if similar survival benefit could be achieved without CN with TKIs since most of pts enrolled into phase III trials had undergone CN. Methods: A total of 270 mRCC pts will be randomized to receiveCN followed by TKIs vs upfront TKIs without CN. Patients will receive pazopanib 800 mg orally daily or sunitinib 50 mg daily, 4 weeks on/ 2 weeks off. The choice of TKI will be done according to investigator’s clinical practice. Primary objective: to compare clinical benefit, as measured by overall survival (OS), provided by CN followed by TKIs vs upfront TKIs in pts with mRCC. Secondary objectives: i) to compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs; ii) Safety; iii) Exploratory analyses: evaluation of the predictive role of circulating tumor cells count and circulating tumor DNA at baseline, before and after surgery (in pts undergoing CN), 24 weeks after randomization and at the time of disease progression. Key inclusion criteria: Favorable or intermediate MSKCC or Heng prognostic risk group; histological diagnosis of RCC with a clear-cell component; resectable asymptomatic mRCC with primary tumor in place; up to three different metastatic sites; ≥ 3 metastatic lesions. Key exclusion criteria: Widespread disease ( > or = 4 metastatic organ sites); disease suitable of metastasectomy ( < 3 lesions confined at one organ site). Statistical plan: The sample size was calculated in order to compare 5-year OS between subjects randomized to receive CN followed by TKIs and those randomized to receive upfront TKIs. A total of 191 deaths will yield 80% power to detect a hazard ratio of 1.5 of upfront TKIs vs CN followed by TKIs with an overall type 1 error of 0.05 (two-sided log-rank test). Such a HR corresponds to an increase in the 5-year OS, from an anticipated value of 10% for TKIs to 21.5% for CN followed by TKIs. To date 10/270 pts have been enrolled. Clinical trial information: NCT02535351.

A FavorAx study of axitinib in favorable risk patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 666-666
Author(s):  
Ilya Tsimafeyeu ◽  
Pavel Borisov ◽  
Ahmed Abdelgafur ◽  
Roman Leonenkov ◽  
Olga Novikova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Primary Endpoint ◽  
Renal Cell ◽  
Response Rate ◽  
Objective Response ◽  
First Line ◽  
History Of

666 Background: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in AXIS study. 75% of patients had intermediate and poor IMDC prognosis. In this phase 2 study, we assessed the activity of axitinib in mRCC patients with favourable risk and a history of prior VEGFR-directed therapy. Methods: Patients were required to have clear cell mRCC, favourable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was PFS. Additional endpoints included response rate, safety, and overall survival (OS). Results: A total of 21 patients were enrolled, 62% of whom were male. Median age was 59 years. 11 (52%) patients had 2 and more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib with a median PFS of 17 months (95% CI 14-20). After a median follow-up of 16 months, the median PFS and OS was not yet reached. The current study did achieve its primary endpoint based on the 10-month PFS of 71.4%. 3 (14.3%) patients had confirmed partial responses and 14 (66.7%) had stable disease. No grade 3/4 treatment-related adverse events were observed; the most frequent grade 1/2 treatment-related adverse events were hypertension (57.1%), fatigue (57.1%), GI (33%) and skin (19%) toxicity. 7 patients had dose-escalation of axitinib and 1 patient had dose reduction. Conclusions: The encouraging PFS and favorable safety profile observed in FavorAx study support the administration of axitinib in mRCC patients with favourable IMDC risk and a history of prior sunitinib or pazopanib. Clinical trial information: NCT02700568.

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