A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC)
Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and pr...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Molina, Ana M. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2013 |
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| Übergeordnetes Werk: |
Enthalten in: Cancer chemotherapy and pharmacology - Berlin : Springer, 1978, 73(2013), 1 vom: 05. Nov., Seite 181-189 |
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| Übergeordnetes Werk: |
volume:73 ; year:2013 ; number:1 ; day:05 ; month:11 ; pages:181-189 |
| Links: |
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| DOI / URN: |
10.1007/s00280-013-2339-y |
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| Katalog-ID: |
SPR003606538 |
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| 100 | 1 | |a Molina, Ana M. |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) |
| 264 | 1 | |c 2013 | |
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| 500 | |a © The Author(s) 2013 | ||
| 520 | |a Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. | ||
| 650 | 4 | |a Lenvatinib |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Everolimus |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Metastatic renal cell carcinoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Antitumor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a mTOR |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a VEGF |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Hutson, Thomas E. |4 aut | |
| 700 | 1 | |a Larkin, James |4 aut | |
| 700 | 1 | |a Gold, Anne M. |4 aut | |
| 700 | 1 | |a Wood, Karen |4 aut | |
| 700 | 1 | |a Carter, Dave |4 aut | |
| 700 | 1 | |a Motzer, Robert |4 aut | |
| 700 | 1 | |a Michaelson, M. Dror |4 aut | |
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10.1007/s00280-013-2339-y doi (DE-627)SPR003606538 (SPR)s00280-013-2339-y-e DE-627 ger DE-627 rakwb eng Molina, Ana M. verfasserin aut A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2013 Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 Hutson, Thomas E. aut Larkin, James aut Gold, Anne M. aut Wood, Karen aut Carter, Dave aut Motzer, Robert aut Michaelson, M. Dror aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 73(2013), 1 vom: 05. Nov., Seite 181-189 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:73 year:2013 number:1 day:05 month:11 pages:181-189 https://dx.doi.org/10.1007/s00280-013-2339-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 73 2013 1 05 11 181-189 |
| spelling |
10.1007/s00280-013-2339-y doi (DE-627)SPR003606538 (SPR)s00280-013-2339-y-e DE-627 ger DE-627 rakwb eng Molina, Ana M. verfasserin aut A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2013 Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 Hutson, Thomas E. aut Larkin, James aut Gold, Anne M. aut Wood, Karen aut Carter, Dave aut Motzer, Robert aut Michaelson, M. Dror aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 73(2013), 1 vom: 05. Nov., Seite 181-189 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:73 year:2013 number:1 day:05 month:11 pages:181-189 https://dx.doi.org/10.1007/s00280-013-2339-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 73 2013 1 05 11 181-189 |
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10.1007/s00280-013-2339-y doi (DE-627)SPR003606538 (SPR)s00280-013-2339-y-e DE-627 ger DE-627 rakwb eng Molina, Ana M. verfasserin aut A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2013 Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 Hutson, Thomas E. aut Larkin, James aut Gold, Anne M. aut Wood, Karen aut Carter, Dave aut Motzer, Robert aut Michaelson, M. Dror aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 73(2013), 1 vom: 05. Nov., Seite 181-189 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:73 year:2013 number:1 day:05 month:11 pages:181-189 https://dx.doi.org/10.1007/s00280-013-2339-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 73 2013 1 05 11 181-189 |
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10.1007/s00280-013-2339-y doi (DE-627)SPR003606538 (SPR)s00280-013-2339-y-e DE-627 ger DE-627 rakwb eng Molina, Ana M. verfasserin aut A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2013 Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 Hutson, Thomas E. aut Larkin, James aut Gold, Anne M. aut Wood, Karen aut Carter, Dave aut Motzer, Robert aut Michaelson, M. Dror aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 73(2013), 1 vom: 05. Nov., Seite 181-189 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:73 year:2013 number:1 day:05 month:11 pages:181-189 https://dx.doi.org/10.1007/s00280-013-2339-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 73 2013 1 05 11 181-189 |
| allfieldsSound |
10.1007/s00280-013-2339-y doi (DE-627)SPR003606538 (SPR)s00280-013-2339-y-e DE-627 ger DE-627 rakwb eng Molina, Ana M. verfasserin aut A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2013 Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 Hutson, Thomas E. aut Larkin, James aut Gold, Anne M. aut Wood, Karen aut Carter, Dave aut Motzer, Robert aut Michaelson, M. Dror aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 73(2013), 1 vom: 05. Nov., Seite 181-189 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:73 year:2013 number:1 day:05 month:11 pages:181-189 https://dx.doi.org/10.1007/s00280-013-2339-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 73 2013 1 05 11 181-189 |
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Enthalten in Cancer chemotherapy and pharmacology 73(2013), 1 vom: 05. Nov., Seite 181-189 volume:73 year:2013 number:1 day:05 month:11 pages:181-189 |
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Enthalten in Cancer chemotherapy and pharmacology 73(2013), 1 vom: 05. Nov., Seite 181-189 volume:73 year:2013 number:1 day:05 month:11 pages:181-189 |
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Lenvatinib Everolimus Metastatic renal cell carcinoma Antitumor mTOR VEGF |
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Cancer chemotherapy and pharmacology |
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Molina, Ana M. @@aut@@ Hutson, Thomas E. @@aut@@ Larkin, James @@aut@@ Gold, Anne M. @@aut@@ Wood, Karen @@aut@@ Carter, Dave @@aut@@ Motzer, Robert @@aut@@ Michaelson, M. Dror @@aut@@ |
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2013-11-05T00:00:00Z |
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Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. 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Molina, Ana M. |
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Molina, Ana M. misc Lenvatinib misc Everolimus misc Metastatic renal cell carcinoma misc Antitumor misc mTOR misc VEGF A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) |
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A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) Lenvatinib (dpeaa)DE-He213 Everolimus (dpeaa)DE-He213 Metastatic renal cell carcinoma (dpeaa)DE-He213 Antitumor (dpeaa)DE-He213 mTOR (dpeaa)DE-He213 VEGF (dpeaa)DE-He213 |
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Molina, Ana M. Hutson, Thomas E. Larkin, James Gold, Anne M. Wood, Karen Carter, Dave Motzer, Robert Michaelson, M. Dror |
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Molina, Ana M. |
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10.1007/s00280-013-2339-y |
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phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (e7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (rcc) |
| title_auth |
A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) |
| abstract |
Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. © The Author(s) 2013 |
| abstractGer |
Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. © The Author(s) 2013 |
| abstract_unstemmed |
Purpose Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Methods Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0–1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Results Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade ≥3: 10 %), mucosal inflammation 50 %, proteinuria (Grade ≥3: 15 %), diarrhea (Grade ≥3: 10 %), vomiting (Grade ≥3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Conclusions Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. © The Author(s) 2013 |
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A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) |
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| score |
7.3998623 |