PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of imatinib, a platelet-derived growth factor-beta receptor antagonist, when added to the combination bevacizumab/erlotinib in the treatment of patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Ninety-four patients with metastatic clear cell renal carcinoma were treated with bevacizumab 10 mg/kg intravenously every 2 weeks, erlotinib 150 mg orally daily, and imatinib 400 mg orally daily. Patients were reevaluated after 8 weeks of treatment; patients with objective response or stable disease (SD) continued to receive treatment until they experienced tumor progression. RESULTS: Fifteen of 88 evaluable patients (17%; 95% confidence interval, 10%-26%) had partial responses, whereas an additional 54 patients (61%) had SD. The median progression-free and overall survival for all patients was 8.9 months and 17.2 months, respectively. The addition of imatinib markedly increased toxicity compared with the bevacizumab/erlotinib regimen; the most common grade 3/4 toxicities were diarrhea, rash, and fatigue. CONCLUSION: Bevacizumab/erlotinib/imatinib was unacceptably toxic in this group of patients. Inhibition of the PDGF receptor (PDGFR) with imatinib did not appear to improve efficacy compared retrospectively with the results of treatment with bevacizumab/erlotinib. The importance of PDGFR inhibition in the treatment of advanced clear cell renal carcinoma remains unclear. Further development of this particular combination is not planned or recommended.
PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of imatinib, a platelet-derived growth factor-beta receptor antagonist, when added to the combination bevacizumab/erlotinib in the treatment of patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Ninety-four patients with metastatic clear cell renal carcinoma were treated with bevacizumab 10 mg/kg intravenously every 2 weeks, erlotinib 150 mg orally daily, and imatinib 400 mg orally daily. Patients were reevaluated after 8 weeks of treatment; patients with objective response or stable disease (SD) continued to receive treatment until they experienced tumor progression. RESULTS: Fifteen of 88 evaluable patients (17%; 95% confidence interval, 10%-26%) had partial responses, whereas an additional 54 patients (61%) had SD. The median progression-free and overall survival for all patients was 8.9 months and 17.2 months, respectively. The addition of imatinib markedly increased toxicity compared with the bevacizumab/erlotinib regimen; the most common grade 3/4 toxicities were diarrhea, rash, and fatigue. CONCLUSION:Bevacizumab/erlotinib/imatinib was unacceptably toxic in this group of patients. Inhibition of the PDGF receptor (PDGFR) with imatinib did not appear to improve efficacy compared retrospectively with the results of treatment with bevacizumab/erlotinib. The importance of PDGFR inhibition in the treatment of advanced clear cell renal carcinoma remains unclear. Further development of this particular combination is not planned or recommended.
Authors: Napoleon Santos; Justin B Wenger; Pamela Havre; Yanxia Liu; Roi Dagan; Iman Imanirad; Alison M Ivey; Robert A Zlotecki; Chester B Algood; Scott M Gilbert; Carmen J Allegra; Paul Okunieff; Johannes Vieweg; Nam H Dang; Hendrik Luesch; Long H Dang Journal: Oncology Date: 2011-11-12 Impact factor: 2.935
Authors: Ana E Paiva; Luiza Lousado; Daniel A P Guerra; Patrick O Azevedo; Isadora F G Sena; Julia P Andreotti; Gabryella S P Santos; Ricardo Gonçalves; Akiva Mintz; Alexander Birbrair Journal: Cancer Res Date: 2018-05-22 Impact factor: 12.701
Authors: Marlies H G Langenberg; Petronella O Witteveen; Nienke A G Lankheet; Jeanine Ml Roodhart; Hilde Rosing; Ingeborg J G M van den Heuvel; Jos H Beijnen; Emile E Voest Journal: Neoplasia Date: 2010-02 Impact factor: 5.715
Authors: Daniel A P Guerra; Ana E Paiva; Isadora F G Sena; Patrick O Azevedo; Walison N Silva; Akiva Mintz; Alexander Birbrair Journal: Angiogenesis Date: 2018-05-14 Impact factor: 9.596