PURPOSE: To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Two groups of patients with metastatic renal cell carcinoma were eligible for this study: those with no previous treatment with targeted agents and those with previous treatment with sunitinib and/or sorafenib. All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. Patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred. RESULTS: Eighty patients (50 untreated, 30 previously treated) entered this clinical trial. The combination of bevacizumab/everolimus showed activity in both groups. Median progression-free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. Overall response rates (30% and 23%) were similar in both groups. The regimen was well tolerated by most patients, with a toxicity profile as expected based on the known toxicities of these two agents. Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients. CONCLUSION: Bevacizumab/everolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as first-line treatment or after treatment with sunitinib and/or sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study.
PURPOSE: To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Two groups of patients with metastatic renal cell carcinoma were eligible for this study: those with no previous treatment with targeted agents and those with previous treatment with sunitinib and/or sorafenib. All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. Patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred. RESULTS: Eighty patients (50 untreated, 30 previously treated) entered this clinical trial. The combination of bevacizumab/everolimus showed activity in both groups. Median progression-free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. Overall response rates (30% and 23%) were similar in both groups. The regimen was well tolerated by most patients, with a toxicity profile as expected based on the known toxicities of these two agents. Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients. CONCLUSION:Bevacizumab/everolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as first-line treatment or after treatment with sunitinib and/or sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study.
Authors: L V Klotz; M E Eichhorn; B Schwarz; H Seeliger; M K Angele; K-W Jauch; Christiane J Bruns Journal: Langenbecks Arch Surg Date: 2012-03-14 Impact factor: 3.445
Authors: Rhonda L Bitting; Patrick Healy; Patricia A Creel; James Turnbull; Karla Morris; Sarah Yenser Wood; Herbert I Hurwitz; Mark D Starr; Andrew B Nixon; Andrew J Armstrong; Daniel J George Journal: Clin Genitourin Cancer Date: 2013-11-14 Impact factor: 2.872
Authors: Shivanni Kummar; Helen X Chen; John Wright; Susan Holbeck; Myrtle Davis Millin; Joseph Tomaszewski; James Zweibel; Jerry Collins; James H Doroshow Journal: Nat Rev Drug Discov Date: 2010-10-29 Impact factor: 84.694
Authors: Joshua E Logan; Edward N Rampersaud; Geoffrey A Sonn; Karim Chamie; Arie S Belldegrun; Allan J Pantuck; Dennis J Slamon; Fairooz F Kabbinavar Journal: Rev Urol Date: 2012
Authors: Kenta Masui; Beatrice Gini; Jill Wykosky; Ciro Zanca; Paul S Mischel; Frank B Furnari; Webster K Cavenee Journal: Carcinogenesis Date: 2013-03-01 Impact factor: 4.944
Authors: John H Strickler; Alexander N Starodub; Jingquan Jia; Kellen L Meadows; Andrew B Nixon; Andrew Dellinger; Michael A Morse; Hope E Uronis; P Kelly Marcom; S Yousuf Zafar; Sherri T Haley; Herbert I Hurwitz Journal: Cancer Chemother Pharmacol Date: 2012-06-29 Impact factor: 3.333
Authors: Rana R McKay; Guillermo De Velasco; Lillian Werner; Joaquim Bellmunt; Lauren Harshman; Christopher Sweeney; Jonathan E Rosenberg; Michelle Hirsch; Sabina Signoretti; Eliezer M Van Allen; Meghara Walsh; Ulka Vaishampayan; David F McDermott; Toni K Choueiri Journal: Cancer Date: 2016-05-19 Impact factor: 6.860