Long-term therapy with sunitinib and sorafenib in patients with metastasizing renal cell carcinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 407-407 ◽  
Author(s):  
S. Richter ◽  
C. Piper ◽  
D. A. Pfister ◽  
B. Brehmer ◽  
A. Heidenreich
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Term Therapy ◽  
Good Tolerability ◽  
Significant Treatment ◽  
Line Therapy ◽  
Long Term Therapy

407 Background: Multitargeted tyrosine kinase inhibitors (MTKIs) constitute the established therapy in patients with metastasizing renal cell carcinoma. There are only few data concerning efficiency and safety, the reasons for a longterm response with good tolerability under MTKIs is still unknown. Methods: We retrospectively analyzed the data of patients (pts.) under long-term therapy (>1 year) with sorafenib or sunitinib. Localization of metastases, number of cycles, sequence of therapy, treatment-associated toxicities, and frequency of dose reductions were our main focus of interest. Results: 15 pts. (14 male, one female) with an mean age of 66,33 (44-81) years, were treated with 19,86 (12-35) cycles of sorafenib or sunitinib. 14/15 pts. underwent radical nephrectomy before the treatment. Localization of metastasis were as follows: pulmonary (9/15), hepatic (4/15), nodal (8/15), osseous (3/15), and pancreatic (2/15). In four pts. two or more organs were affected, in six pts. only one organ. As a first-line therapy nine pts. received sunitinib for 20.67 (12-35) cycles and one patient sorafenib for 44 cycles. For second line therapy two pts. were treated with sunitinib for 13 (12-14) cycles and three pts. with sorafenib for 23.33 (18-28) cycles. In five pts. a dose reduction of 25-50% was necessary due to significant treatment associated side effects, afterwards toxicities were tolerable under long term therapy (grade 1 in 10 pts.). Conclusions: The results show, that longterm therapy with sunitinib or sorafenib is tolerable and efficacious independent on previous treatment. Prognostic factors concerning longterm response and low toxicity profile at a molecular biological level are still unknown, further investigations are of importance and are currently performed at our institution. No significant financial relationships to disclose.

scholarly journals The Role of Everolimus in Renal Cell Carcinoma

2015 ◽  
Vol 2 (4) ◽  
pp. 187-194
Author(s):  
Malek Meskawi ◽  
Roger Valdivieso ◽  
Paolo Dell’Oglio ◽  
Vincent Trudeau ◽  
Alessandro Larcher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Phase Iii ◽  
Current Evidence ◽  
Second Line ◽  
Cell Renal Cell Carcinoma ◽  
Line Therapy

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

Multi-Institutional Study of the Angiogenesis Inhibitor TNP-470 in Metastatic Renal Carcinoma

1999 ◽  
Vol 17 (8) ◽  
pp. 2541-2541 ◽  
Author(s):  
Walter M. Stadler ◽  
Timothy Kuzel ◽  
Charles Shapiro ◽  
Jeffery Sosman ◽  
Joseph Clark ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Regression ◽  
Angiogenesis Inhibitor ◽  
Term Therapy ◽  
Prior Therapy ◽  
Previously Treated Patients ◽  
Long Term Therapy

PURPOSE: Renal cell carcinoma is resistant to most chemotherapy, and only a minority of patients respond to immunotherapy. Its highly vascular nature suggests that antiangiogenesis therapy might be useful. We thus performed a phase II study of the fumigillin analog TNP-470 in previously treated patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Metastatic renal cell carcinoma patients with good organ function were entered onto the study through five separate institutions. There were no exclusion criteria for prior therapy. All patients were treated at a dose of 60 mg/m2 of TNP-470 infused over 1 hour three times per week. RESULTS: Thirty-three patients were enrolled. Therapy was generally well tolerated, but asthenia, fatigue, vertigo, dizziness, sense of imbalance, and loss of concentration were common and severe enough to lead to therapy discontinuation in five patients. There was only one partial response of short duration (response rate, 3%, 95% confidence interval, 0% to 16%), but six patients (18%) remained on study for 6 or more months without toxicity or disease progression. CONCLUSION: Long-term therapy with TNP-470 has manageable toxicities and is feasible in patients with metastatic renal cell carcinoma but does not lead to any significant objective responses. Further studies in this population using TNP-470 schedules that produce more prolonged drug levels and clinical trial end points other than objective tumor regression may be indicated.

Long progression-free survival with cabozantinib in a heavily pretreated patient with metastatic renal cell carcinoma: a case report

2021 ◽  
pp. 030089162199073
Author(s):  
Cecilia Nasso ◽  
Roberto Sabbatini ◽  
Cinzia Baldessari ◽  
Massimo Dominici ◽  
Maria Giuseppa Vitale
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Heavily Pretreated ◽  
Pretreated Patients

Renal cell carcinoma accounts for 3% of all tumors. Over the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has improved owing to the approval of several drugs such as tyrosine kinase inhibitors and immunotherapy. The median progression-free survival (PFS) does not exceed 8 months with the available drugs in pretreated patients with mRCC. We present a case of a patient with a long-term response to fourth-line treatment with cabozantinib. Our patient obtained a PFS of 33 months, which is much higher than that reported in literature.

Efficacy and safety of sequential use of everolimus in patients with metastatic renal cell carcinoma previously treated by bevacizumab with or without interferon therapy: Results from pooled analysis of AVATOR, CHANGE, and TRAIN studies.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 585-585
Author(s):  
Antoine Thiery- Vuillemin ◽  
Aline Guillot ◽  
Thomas Steiner ◽  
Edwin Herrmann ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Pooled Analysis ◽  
Second Line ◽  
Line Therapy

585 Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients (pts) with mRCC. AVATOR was the 1st study to explore the sequential use of bevacizumab followed by everolimus but with limited number of pts. Methods: In order to further explore this sequence pooled data from the AVATOR, CHANGE and TRAIN studies were analysed retrospectively. All pts had mRCC and were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus time to progression (TTP). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence, everolimus treatment and safety. Results: 89 pts were included in the analysis. Median age was 68 years [18-90]. At everolimus initiation ECOG was 0-1 for 72% pts and 16% were classified as poor prognosis from Heng classification. Exploring the duration of second-line everolimus treatment, 32% of patients received less than 3 months of everolimus and 35% received at least 6 months of treatment. At the time of data analysis, 20 pts (24%) were still receiving everolimus. Pts receiving everolimus after bevacizumab experienced a median TTP of 6 months [95%CI 4 - 14]. Median OS was not reached for everolimus second-line therapy. At 36 months after the start of first-line therapy, 60.4% of pts were still alive. All grades of common adverse events were consistent with the known safety profile of everolimus. Conclusions: The larger size of this cohort confirms the signal previously seen with AVATOR that the sequence of bevacizumab followed by everolimus displays interesting efficacy with not unexpected toxicity from everolimus and compares favourably with RECORD-1.

scholarly journals Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma

2015 ◽  
Vol 26 (2) ◽  
pp. 378-385 ◽  
Author(s):  
R. Elaidi ◽  
A. Harbaoui ◽  
B. Beuselinck ◽  
J.-C. Eymard ◽  
A. Bamias ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

scholarly journals Extended Disease Control with Unconventional Cabozantinib Dose Increase in Metastatic Renal Cell Carcinoma

Kidney Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Akanksha Sharma ◽  
Roy Elias ◽  
Alana Christie ◽  
Noelle S. Williams ◽  
Ivan Pedrosa ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Medical Center ◽  
Treatment Options ◽  
Good Tolerability

BACKGROUND: Cabozantinib is among the most potent tyrosine kinase inhibitors (TKIs) FDA-approved for metastatic renal cell carcinoma (mRCC). Effective treatments after progression on cabozantinib salvage therapy are limited. Dose escalation for other TKIs has been shown to afford added disease control. OBJECTIVE: We sought to evaluate whether dose escalation of cabozantinib (Cabometyx®) from conventional doses in selected patients with limited treatment options offered additional disease control. We asked how cabozantinib dose increases may affect circulating drug levels. METHODS: We identified patients with mRCC at the University of Texas Southwestern Medical Center who were treated with cabozantinib dose escalation to 80 mg after progressing on conventional cabozantinib 60 mg. We then queried leading kidney cancer investigators across the world to identify additional patients. Finally, we reviewed pharmacokinetic (PK) data to assess how higher doses impacted circulating levels by comparison to other formulations (Cometriq® capsules). RESULTS: We report six patients treated at two different institutions with cabozantinib-responsive disease and good tolerability, where cabozantinib was dose escalated (typically to 80mg, but as high as 120 mg) after progression on 60 mg, a strategy that resulted in added disease control (median duration, 14 months; 95% Confidence Interval [CI]: 8 –Not Estimable[NE]). Four patients (66.7%) had disease control lasting at least 1 year. No grade III/IV adverse events were identified. A comparison of PK data to FDA-approved cabozantinib 140 mg capsules suggest that cabozantinib 80 mg tablets results in comparable exposures. CONCLUSIONS: mRCC patients with cabozantinib responsive disease and reasonable tolerability may benefit from dose escalation at progression.

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