scholarly journals Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma

Kidney Cancer ◽  
2019 ◽  
Vol 3 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Andreas Bruchbacher ◽  
Sebastian Nachbargauer ◽  
Harun Fajkovic ◽  
Manuela Schmidinger
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell

scholarly journals Dose escalation of axitinib on disease progression as a strategy in the treatment of metastatic renal cell carcinoma

ESMO Open ◽  
2018 ◽  
Vol 3 (7) ◽  
pp. e000445 ◽  
Author(s):  
Gary Joseph Doherty ◽  
Deirdre Lynskey ◽  
Athena Matakidou ◽  
Kate Fife ◽  
Tim Eisen
Keyword(s):  
Renal Cell Carcinoma ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Drug Label ◽  
Entire Cohort

IntroductionThe AXIS trial established axitinib as a standard of care treatment for patients with metastatic renal cell carcinoma (mRCC) after failure of a prior tyrosine kinase inhibitor. Axitinib dosing begins at 5  mg twice daily, with escalation of doses to 7  and 10  mg after consecutive 2-week intervals if tolerated (as per the drug label). Given clinical concerns about drug-related toxicity, we have used a pragmatic strategy where dose escalations were made only after disease progression or where rapid responses were clinically required.MethodsWe performed a retrospective review of electronic health records and radiology of all patients with mRCC treated with axitinib for >2 weeks at Addenbrooke’s Hospital, Cambridge, UK, over a 37 -month period to determine the clinical and radiological effects of dose escalations made according to the above strategy.Results42 patients fitting these criteria were identified, 29 having ≥1  dose escalation event (DEE). 60 DEEs were identified (median of two per patient), and the objective radiological consequences of 53 DEEs could be evaluated. The disease control rate (partial response or stable disease) after the first DEE instituted for disease progression was similar to that after the second DEE (68.8% vs 70%). 56.6 % of all DEEs and 63.6 % of DEEs made as a result of disease progression resulted in disease control. The median OS from the commencement of axitinib for all dose-escalated patients was 19.9 months, and 16.5 months for the entire cohort. The mean dose (for all patients) at 90 days after starting axitinib was 5.92  mg.ConclusionThese data suggest that dose escalation of axitinib after disease progression may be an effective dosing strategy for patients with mRCC, and this may be a preferred option in patients in whom there are particular concerns about drug-related toxicity, quality of life optimisation or healthcare-associated costs.

scholarly journals Sunitinib rechallenge with dose escalation in progressive metastatic renal cell carcinoma

Medicine ◽  
2018 ◽  
Vol 97 (31) ◽  
pp. e11565 ◽  
Author(s):  
Xingming Zhang ◽  
Pengfei Shen ◽  
Jin Yao ◽  
Ni Chen ◽  
Jiyan Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell

scholarly journals An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti‐Endoglin Antibody) with Axitinib in Patients with Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 24 (2) ◽  
pp. 202-210 ◽  
Author(s):  
Toni K. Choueiri ◽  
M. Dror Michaelson ◽  
Edwin M. Posadas ◽  
Guru P. Sonpavde ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Open Label ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Open Label Phase

Clinical Effect of Dose Escalation After Disease Progression in Patients With Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 15 (2) ◽  
pp. e275-e280 ◽  
Author(s):  
Moshe C. Ornstein ◽  
Laura Wood ◽  
Paul Elson ◽  
Kimberly Allman ◽  
Jennifer Beach ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Clinical Effect

A phase I study of BMS-936558 plus sunitinib or pazopanib in patients with metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2614-TPS2614
Author(s):  
Hans J. Hammers ◽  
Brian I. Rini ◽  
Gary R. Hudes ◽  
Marc S. Ernstoff ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Phase I Study ◽  
Predictive Biomarkers ◽  
Treatment Naïve

TPS2614 Background: Standard treatments for metastatic renal cell carcinoma (mRCC) block the vascular endothelial growth factor pathway (eg, sunitinib, pazopanib) or mammalian target of rapamycin pathway (e.g., temsirolimus, everolimus). However, most patients (pts) develop resistance and complete responses are rare. Upregulation of programmed death-1 (PD-1) in tumor infiltrating lymphoctyes, and its ligand PD-L1 in tumors, is associated with more aggressive disease and poor prognosis. Blocking the PD-1/PD-L1 interaction is a novel immunotherapeutic approach for mRCC. In preliminary results of a phase I trial, the anti-PD-1 monoclonal antibody BMS-936558 had antitumor activity in pts with advanced tumors, including objective responses (ORs) in 6 of 18 pts with mRCC. Here we describe a phase I study planned to evaluate the safety, tolerability, and maximum tolerated dose (MTD) of BMS-936558, when combined with sunitinib or pazopanib in pts with mRCC. Methods: This open-label study will have two parallel treatment arms (BMS-936558 plus sunitinib and BMS-936558 plus pazopanib) conducted in two parts (dose escalation and dose expansion). Pts must have received ≥1 prior systemic therapy to be eligible for dose escalation. Only treatment-naïve pts will be eligible for dose expansion. Up to 36 pts (18 per arm) will be treated in the dose-escalation phase. After determining the MTD of BMS-936558, treatment-naïve pts will be enrolled to expansion cohorts allowing 24 pts to be treated at the MTD of each arm. Each treatment cycle will be 6 weeks, with BMS-936558 dosed on Days 1 and 22 and sunitinib or pazopanib given according to product label. Adverse events will be graded according to NCI CTCAE v4.0. Disease will be assessed every 6 weeks for the first four assessments and then every 12 weeks until disease progression. Pts will be treated until unacceptable toxicity, disease progression, or withdrawal of consent. The safety profile in pts treated at the MTD will be used to determine the recommended phase II study dose of BMS-936558 in each combination arm. Secondary objectives will include OR rate and duration of response based on RECIST 1.1. Exploratory analyses will investigate predictive biomarkers of BMS-936558.

Clinical effect of TKI dose-escalation after disease progression in patients with metastatic renal cell carcinoma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
Moshe Chaim Ornstein ◽  
Paul Elson ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Laura S. Wood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Clinical Effect

A novel strategy for axitinib dosing in the treatment of metastatic renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 464-464
Author(s):  
Gary Doherty ◽  
Deirdre Lynskey ◽  
Athena Matakidou ◽  
Kate Fife ◽  
Tim Eisen
Keyword(s):  
Renal Cell Carcinoma ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Survival Data ◽  
Renal Cell ◽  
Drug Exposure ◽  
Dosing Strategy

464 Background: The AXIS trial established axitinib as an effective second line treatment for patients with metastatic renal cell carcinoma (mRCC). The dosing schedule of axitinib in this trial begins at 5mg twice daily, with escalation of individual doses to 7mg and 10mg after consecutive 2 week intervals if tolerated. We observed significant drug-related toxicity using this dosing strategy, particularly after dose escalations, while clinical responses were often observed at the starting dose. We therefore switched to a pragmatic strategy where dose escalations were made only after disease progression or where a rapid response was deemed clinically pertinent. Methods: We performed a retrospective review of electronic health records and radiology of all patients with mRCC treated with axitinib for greater than 2 weeks at Addenbrooke’s Hospital, Cambridge, UK (a tertiary referral center), over a 40 month period to determine the clinical and radiological effects of dose escalations made according to the above strategy. Results: 42 patients fitting these criteria were identified; of these, 29 had at least one dose escalation event (DEE). A total of 58 DEEs were identified, with a median of 2 per patient, and the objective radiological consequences of 50 of these could be determined. The disease control rate (partial response or stable disease) after the first DEE instituted for disease progression was similar to that after the second DEE (68.8% versus 70%). 56% of all DEEs, and 62.5% of DEEs made as a result of disease progression, resulted in disease control. The median overall survival from the commencement of axitinib for all dose-escalated patients was 19.9 months, and 6.7 months for non-dose-escalated patients. The median survival for dose-escalated patients with a higher than median time on a prior tyrosine kinase inhibitor has not been reached at the time of data cut-off. The mean dose (for all patients) at 90 days after starting axitinib was 5.92 mg. Conclusions: These data suggest that dose escalation of axitinib after disease progression may be an effective dosing strategy for patients with mRCC, and may reduce toxicity through lower drug exposure. Our survival data compares favourably to the AXIS trial in a real practice population.

Sunitinib dose escalation after disease progression in metastatic renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 458-458
Author(s):  
Jacques Raphael ◽  
Alia Thawer ◽  
Georg A. Bjarnason
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Skin Toxicity ◽  
Kaplan Meier ◽  
Best Response ◽  
Higher Doses

458 Background: Previous pharmacologic studies demonstrated that higher sunitinib ( S) exposure is associated with improved clinical outcomes in metastatic renal cell carcinoma (mRCC) patients. We aimed to assess the efficacy and toxicity of S dose escalation in mRCC patients progressing on the standard 50mg dose. Methods: A single institution retrospective review was conducted on mRCC patients, treated outside trials with a 50 mg S dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. At progression, patients were dose escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted. Median Progression and Overall Survival (PFS, OS) were analyzed using the Kaplan Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose escalation and second progression respectively. Results: Twenty-five eligible patients were identified, with a median follow-up of 40.3 months (11.1-66.6) and a mean age of 54 years (12.4). The majority of patients underwent cytoreductive surgery (92%) and were men (88%). Thirty two percent, 44%, and 24% had a good, intermediate, and poor prognostic Heng score respectively. At the 50 mg doses, 60% and 16% of patients had a partial response (PR) and stable disease (SD) respectively with a median time to progression (TTP) of 11.4 months (95% CI, 3-20.7). After progression, 36% and 28% had PR and SD on higher doses of S respectively with a TTP of 7.8 months (95% CI, 6.3-12.4). Three patients with progressive disease as best response on a 50 mg S dose achieved SD (2/3) or PR (1/3) after dose escalation. The median PFS1, PFS2, and OS were 6.1 months (95% CI, 2.3-19.4), 6.7 months (95% CI, 3.1-8.4), and 63.7 months (95% CI, 26-not reached) respectively. The most common adverse events after dose escalation were fatigue (56%), diarrhea (40%), and skin toxicity (28%). Conclusions: Patients with mRCC who progress on a 50 mg S dose, may derive a clinical benefit and prolonged survival from dose escalation with acceptable toxicity profiles. These results need to be confirmed in well-designed prospective studies with the aim to optimize the duration of benefit from S therapy.

scholarly journals Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial

2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Katrien De Wolf ◽  
Sylvie Rottey ◽  
Karim Vermaelen ◽  
Karel Decaestecker ◽  
Nora Sundahl ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
High Dose ◽  
Dose Radiation
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