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Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation

BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however...

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Autores principales: Staehler, M, Haseke, N, Roosen, A, Stadler, T, Bader, M, Siebels, M, Karl, A, Stief, CG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351952/
https://www.ncbi.nlm.nih.gov/pubmed/20696639
http://dx.doi.org/10.1186/2047-783X-15-7-287
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author Staehler, M
Haseke, N
Roosen, A
Stadler, T
Bader, M
Siebels, M
Karl, A
Stief, CG
author_facet Staehler, M
Haseke, N
Roosen, A
Stadler, T
Bader, M
Siebels, M
Karl, A
Stief, CG
author_sort Staehler, M
collection PubMed
description BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC. METHODS: Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m(2), doxorubicine 50 mg/m(2 )administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction. CONCLUSIONS: Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted.
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spelling pubmed-33519522012-05-16 Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation Staehler, M Haseke, N Roosen, A Stadler, T Bader, M Siebels, M Karl, A Stief, CG Eur J Med Res Research BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC. METHODS: Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m(2), doxorubicine 50 mg/m(2 )administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction. CONCLUSIONS: Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted. BioMed Central 2010-07-26 /pmc/articles/PMC3351952/ /pubmed/20696639 http://dx.doi.org/10.1186/2047-783X-15-7-287 Text en Copyright ©2010 I. Holzapfel Publishers
spellingShingle Research
Staehler, M
Haseke, N
Roosen, A
Stadler, T
Bader, M
Siebels, M
Karl, A
Stief, CG
Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title_full Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title_fullStr Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title_full_unstemmed Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title_short Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation
title_sort sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell carcinoma: a prospective evaluation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351952/
https://www.ncbi.nlm.nih.gov/pubmed/20696639
http://dx.doi.org/10.1186/2047-783X-15-7-287
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