The Experts below are selected from a list of 37035 Experts worldwide ranked by ideXlab platform
Bernard Escudier - One of the best experts on this subject based on the ideXlab platform.
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Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma
The Journal of urology, 2009Co-Authors: M. P. Sablin, Sylvie Négrier, Alain Ravaud, Stéphane Oudard, C. Balleyguier, J. Gautier, C. Celier, Jacques Medioni, Bernard EscudierAbstract:Purpose: Sorafenib and sunitinib are 2 tyrosine kinase inhibitors that were recently approved for renal cell carcinoma. In many patients sequential administration of the 2 drugs occurs because of the lack of sustained efficacy of the first agent. We determined the efficacy and safety of sequential administration.Materials and Methods: To determine whether cross-resistance occurs between these 2 drugs we analyzed the outcome in 90 consecutive patients with renal cell carcinoma from 4 sites in France who had received the 2 drugs sequentially. All patients received Sorafenib followed by sunitinib or vice versa. From 2003 to 2006, 68 patients received Sorafenib, while 22 received sunitinib first.Results: In the Sorafenib-sunitinib group median progression-free survival was 26 weeks with Sorafenib and 28 with sunitinib. In the sunitinib-Sorafenib group median progression-free survival was 22 weeks with sunitinib and 17 with Sorafenib. Median overall survival was 135 weeks in the Sorafenib-sunitinib group and 8...
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randomized phase ii trial of first line treatment with Sorafenib versus interferon alfa 2a in patients with metastatic renal cell carcinoma
Journal of Clinical Oncology, 2009Co-Authors: Bernard Escudier, Sylvie Négrier, C Szczylik, Thomas E Hutson, Tomasz Demkow, Michael Staehler, Frederic Rolland, Nicole Laferriere, Urban J Scheuring, David CellaAbstract:Purpose An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with Sorafenib versus interferon alfa-2a (IFN-α-2a) in patients with untreated, advanced renal cancer. Patients and Methods A total of 189 patients were randomly assigned to oral Sorafenib 400 mg twice daily or to subcutaneous IFN-α-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFN-α-2a patients who progressed were switched to Sorafenib 400 mg twice daily (period 2). Results In period 1 PFS was similar for Sorafenib-treated (n = 97; 5.7 months) and IFN-α-2a–treated patients (n = 92; 5.6 months); more Sorafenib-treated patients had tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades ≥ 3) for Sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFN-α-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2...
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Sorafenib in advanced clear cell renal cell carcinoma
The New England Journal of Medicine, 2007Co-Authors: Bernard Escudier, Sylvie Négrier, Stéphane Oudard, Tim Eisen, Walter M Stadler, Cezary Szczylik, Michael Siebels, Christine Chevreau, Ewa Solska, Apurva A DesaiAbstract:Background We conducted a phase 3, randomized, double-blind, placebo-controlled trial of Sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. Methods From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral Sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received Sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of Sorafenib over placebo. Consequently, crossover was permitted from placebo to Sorafenib, beginning in May 2005. Results At the January 2005 cutoff, the median progression-free survival was 5.5 months in the Sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the Sorafenib group, 0.44;...
Yong Teng - One of the best experts on this subject based on the ideXlab platform.
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fgf19 fgfr4 signaling contributes to the resistance of hepatocellular carcinoma to Sorafenib
Journal of Experimental & Clinical Cancer Research, 2017Co-Authors: Yao Liang Tang, Chienan A Hu, Shuang Huang, Xuli Wang, Yong TengAbstract:Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to Sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to Sorafenib therapy. FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9. Protein levels of FGF19, FGFR4 and c-PARP in various HCC cell lines were measured by Western blotting analysis. Cell viability was determined by MTS assay, apoptosis was determined by DAPI nuclear staining and Western blot of c-PRAP, and ROS generation was determined by DCFH-DA staining and electrochemical biosensor. We showed that FGF19, when overexpressed, inhibited the effect of Sorafenib on ROS generation and apoptosis in HCC. In contrast, loss of FGF19 or its receptor FGFR4 led to a remarkable increase in Sorafenib-induced ROS generation and apoptosis. In addition, knockdown of FGF19 in Sorafenib-resistant HCC cells significantly enhanced the sensitivity to Sorafenib. Importantly, targeting FGF19/FGFR4 axis by ponatinib, a third-generation inhibitor of chronic myeloid leukemia, overcomes HCC resistance of Sorafenib by enhancing ROS-associated apoptosis in Sorafenib-treated HCC. Our results provide the first evidence that inhibition of FGF19/FGFR4 signaling significantly overcomes Sorafenib resistance in HCC. Co-treatment of ponatinib and sorafinib may represent an effective therapeutic approach for eradicating HCC.
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FGF19/FGFR4 signaling contributes to the resistance of hepatocellular carcinoma to Sorafenib
Journal of Experimental & Clinical Cancer Research, 2017Co-Authors: Xuli Wang, Yao Liang Tang, Chienan A Hu, Shuang Huang, Yong TengAbstract:Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to Sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to Sorafenib therapy. FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9. Protein levels of FGF19, FGFR4 and c-PARP in various HCC cell lines were measured by Western blotting analysis. Cell viability was determined by MTS assay, apoptosis was determined by DAPI nuclear staining and Western blot of c-PRAP, and ROS generation was determined by DCFH-DA staining and electrochemical biosensor. We showed that FGF19, when overexpressed, inhibited the effect of Sorafenib on ROS generation and apoptosis in HCC. In contrast, loss of FGF19 or its receptor FGFR4 led to a remarkable increase in Sorafenib-induced ROS generation and apoptosis. In addition, knockdown of FGF19 in Sorafenib-resistant HCC cells significantly enhanced the sensitivity to Sorafenib. Importantly, targeting FGF19/FGFR4 axis by ponatinib, a third-generation inhibitor of chronic myeloid leukemia, overcomes HCC resistance of Sorafenib by enhancing ROS-associated apoptosis in Sorafenib-treated HCC. Our results provide the first evidence that inhibition of FGF19/FGFR4 signaling significantly overcomes Sorafenib resistance in HCC. Co-treatment of ponatinib and sorafinib may represent an effective therapeutic approach for eradicating HCC.
Xuli Wang - One of the best experts on this subject based on the ideXlab platform.
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fgf19 fgfr4 signaling contributes to the resistance of hepatocellular carcinoma to Sorafenib
Journal of Experimental & Clinical Cancer Research, 2017Co-Authors: Yao Liang Tang, Chienan A Hu, Shuang Huang, Xuli Wang, Yong TengAbstract:Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to Sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to Sorafenib therapy. FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9. Protein levels of FGF19, FGFR4 and c-PARP in various HCC cell lines were measured by Western blotting analysis. Cell viability was determined by MTS assay, apoptosis was determined by DAPI nuclear staining and Western blot of c-PRAP, and ROS generation was determined by DCFH-DA staining and electrochemical biosensor. We showed that FGF19, when overexpressed, inhibited the effect of Sorafenib on ROS generation and apoptosis in HCC. In contrast, loss of FGF19 or its receptor FGFR4 led to a remarkable increase in Sorafenib-induced ROS generation and apoptosis. In addition, knockdown of FGF19 in Sorafenib-resistant HCC cells significantly enhanced the sensitivity to Sorafenib. Importantly, targeting FGF19/FGFR4 axis by ponatinib, a third-generation inhibitor of chronic myeloid leukemia, overcomes HCC resistance of Sorafenib by enhancing ROS-associated apoptosis in Sorafenib-treated HCC. Our results provide the first evidence that inhibition of FGF19/FGFR4 signaling significantly overcomes Sorafenib resistance in HCC. Co-treatment of ponatinib and sorafinib may represent an effective therapeutic approach for eradicating HCC.
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FGF19/FGFR4 signaling contributes to the resistance of hepatocellular carcinoma to Sorafenib
Journal of Experimental & Clinical Cancer Research, 2017Co-Authors: Xuli Wang, Yao Liang Tang, Chienan A Hu, Shuang Huang, Yong TengAbstract:Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to Sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to Sorafenib therapy. FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9. Protein levels of FGF19, FGFR4 and c-PARP in various HCC cell lines were measured by Western blotting analysis. Cell viability was determined by MTS assay, apoptosis was determined by DAPI nuclear staining and Western blot of c-PRAP, and ROS generation was determined by DCFH-DA staining and electrochemical biosensor. We showed that FGF19, when overexpressed, inhibited the effect of Sorafenib on ROS generation and apoptosis in HCC. In contrast, loss of FGF19 or its receptor FGFR4 led to a remarkable increase in Sorafenib-induced ROS generation and apoptosis. In addition, knockdown of FGF19 in Sorafenib-resistant HCC cells significantly enhanced the sensitivity to Sorafenib. Importantly, targeting FGF19/FGFR4 axis by ponatinib, a third-generation inhibitor of chronic myeloid leukemia, overcomes HCC resistance of Sorafenib by enhancing ROS-associated apoptosis in Sorafenib-treated HCC. Our results provide the first evidence that inhibition of FGF19/FGFR4 signaling significantly overcomes Sorafenib resistance in HCC. Co-treatment of ponatinib and sorafinib may represent an effective therapeutic approach for eradicating HCC.
Hirotsugu Uemura - One of the best experts on this subject based on the ideXlab platform.
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Sorafenib rechallenge in patients with metastatic renal cell carcinoma.
BJU international, 2012Co-Authors: Masahiro Nozawa, Yutaka Yamamoto, Takafumi Minami, Nobutaka Shimizu, Yuji Hatanaka, Hidenori Tsuji, Hirotsugu UemuraAbstract:What's known on the subject? and What does the study add? Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, Sorafenib and sunitinib, have been reported to show little cross-resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients. This case series shows that patients once refractory to Sorafenib could regain disease control on rechallenge with Sorafenib during sequential treatment. Outcomes of the Sorafenib rechallenge were not significantly affected by the response to the initial Sorafenib treatment or by the duration of intervening treatments between first Sorafenib and rechallenge. To investigate clinical outcomes of Sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC). Patients with metastatic RCC who received Sorafenib rechallenge after failed treatment first with Sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression-free survival (PFS), and adverse events (AEs). Of the 14 patients who received Sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon-α (nine patients) and interleukin-2 (six patients), with a median duration of 9 months. The best responses after the first Sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial Sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients. Rechallenge with Sorafenib was undertaken after a 7.6 month median interval from the initial Sorafenib challenge. Eight patients achieved SD on Sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8-7.0) months. The outcome of the Sorafenib rechallenge was not significantly affected by the response to the initial Sorafenib treatment or by the duration of treatments received between first Sorafenib and rechallenge. No severe AE was newly observed on the rechallenge. In the systemic treatment of advanced RCC, it was suggested that patients once refractory to Sorafenib could regain disease control on rechallenge with Sorafenib during sequential treatment. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.
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Sorafenib rechallenge in patients with metastatic renal cell carcinoma.
BJUI, 2012Co-Authors: Masahiro Nozawa, Yutaka Yamamoto, Takafumi Minami, Nobutaka Shimizu, Yuji Hatanaka, Hidenori Tsuji, Hirotsugu UemuraAbstract:UNLABELLED: What's known on the subject? and What does the study add? Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, Sorafenib and sunitinib, have been reported to show little cross-resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients. This case series shows that patients once refractory to Sorafenib could regain disease control on rechallenge with Sorafenib during sequential treatment. Outcomes of the Sorafenib rechallenge were not significantly affected by the response to the initial Sorafenib treatment or by the duration of intervening treatments between first Sorafenib and rechallenge. OBJECTIVE: To investigate clinical outcomes of Sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC who received Sorafenib rechallenge after failed treatment first with Sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression-free survival (PFS), and adverse events (AEs). RESULTS: Of the 14 patients who received Sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon-α (nine patients) and interleukin-2 (six patients), with a median duration of 9 months. The best responses after the first Sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial Sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients. Rechallenge with Sorafenib was undertaken after a 7.6 month median interval from the initial Sorafenib challenge. Eight patients achieved SD on Sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8-7.0) months. The outcome of the Sorafenib rechallenge was not significantly affected by the response to the initial Sorafenib treatment or by the duration of treatments received between first Sorafenib and rechallenge. No severe AE was newly observed on the rechallenge. CONCLUSION: In the systemic treatment of advanced RCC, it was suggested that patients once refractory to Sorafenib could regain disease control on rechallenge with Sorafenib during sequential treatment.
Sylvie Négrier - One of the best experts on this subject based on the ideXlab platform.
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Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma
The Journal of urology, 2009Co-Authors: M. P. Sablin, Sylvie Négrier, Alain Ravaud, Stéphane Oudard, C. Balleyguier, J. Gautier, C. Celier, Jacques Medioni, Bernard EscudierAbstract:Purpose: Sorafenib and sunitinib are 2 tyrosine kinase inhibitors that were recently approved for renal cell carcinoma. In many patients sequential administration of the 2 drugs occurs because of the lack of sustained efficacy of the first agent. We determined the efficacy and safety of sequential administration.Materials and Methods: To determine whether cross-resistance occurs between these 2 drugs we analyzed the outcome in 90 consecutive patients with renal cell carcinoma from 4 sites in France who had received the 2 drugs sequentially. All patients received Sorafenib followed by sunitinib or vice versa. From 2003 to 2006, 68 patients received Sorafenib, while 22 received sunitinib first.Results: In the Sorafenib-sunitinib group median progression-free survival was 26 weeks with Sorafenib and 28 with sunitinib. In the sunitinib-Sorafenib group median progression-free survival was 22 weeks with sunitinib and 17 with Sorafenib. Median overall survival was 135 weeks in the Sorafenib-sunitinib group and 8...
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randomized phase ii trial of first line treatment with Sorafenib versus interferon alfa 2a in patients with metastatic renal cell carcinoma
Journal of Clinical Oncology, 2009Co-Authors: Bernard Escudier, Sylvie Négrier, C Szczylik, Thomas E Hutson, Tomasz Demkow, Michael Staehler, Frederic Rolland, Nicole Laferriere, Urban J Scheuring, David CellaAbstract:Purpose An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with Sorafenib versus interferon alfa-2a (IFN-α-2a) in patients with untreated, advanced renal cancer. Patients and Methods A total of 189 patients were randomly assigned to oral Sorafenib 400 mg twice daily or to subcutaneous IFN-α-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFN-α-2a patients who progressed were switched to Sorafenib 400 mg twice daily (period 2). Results In period 1 PFS was similar for Sorafenib-treated (n = 97; 5.7 months) and IFN-α-2a–treated patients (n = 92; 5.6 months); more Sorafenib-treated patients had tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades ≥ 3) for Sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFN-α-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2...
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Sorafenib in advanced clear cell renal cell carcinoma
The New England Journal of Medicine, 2007Co-Authors: Bernard Escudier, Sylvie Négrier, Stéphane Oudard, Tim Eisen, Walter M Stadler, Cezary Szczylik, Michael Siebels, Christine Chevreau, Ewa Solska, Apurva A DesaiAbstract:Background We conducted a phase 3, randomized, double-blind, placebo-controlled trial of Sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. Methods From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral Sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received Sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of Sorafenib over placebo. Consequently, crossover was permitted from placebo to Sorafenib, beginning in May 2005. Results At the January 2005 cutoff, the median progression-free survival was 5.5 months in the Sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the Sorafenib group, 0.44;...
