A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors

Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (m...
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Autor*in:	Park, Haeseong [verfasserIn] Williams, Kerry [verfasserIn] Trikalinos, Nikolaos A. [verfasserIn] Larson, Sarah [verfasserIn] Tan, Benjamin [verfasserIn] Waqar, Saiama [verfasserIn] Suresh, Rama [verfasserIn] Morgensztern, Daniel [verfasserIn] Van Tine, Brian A. [verfasserIn] Govindan, Ramaswamy [verfasserIn] Luo, Jingqin [verfasserIn] Lockhart, A. Craig [verfasserIn] Wang-Gillam, Andrea [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	mTOR inhibitor EGFR inhibitor Phase 1 study

Übergeordnetes Werk:	Enthalten in: Cancer chemotherapy and pharmacology - Berlin : Springer, 1978, 87(2020), 3 vom: 06. Nov., Seite 337-347
Übergeordnetes Werk:	volume:87 ; year:2020 ; number:3 ; day:06 ; month:11 ; pages:337-347

Links:	Volltext

DOI / URN:	10.1007/s00280-020-04183-0

Katalog-ID:	SPR043209629

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520			\|a Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263).
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700	1		\|a Wang-Gillam, Andrea \|e verfasserin \|4 aut
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publishDate	2020
allfields	10.1007/s00280-020-04183-0 doi (DE-627)SPR043209629 (DE-599)SPRs00280-020-04183-0-e (SPR)s00280-020-04183-0-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Park, Haeseong verfasserin aut A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213 Williams, Kerry verfasserin aut Trikalinos, Nikolaos A. verfasserin aut Larson, Sarah verfasserin aut Tan, Benjamin verfasserin aut Waqar, Saiama verfasserin aut Suresh, Rama verfasserin aut Morgensztern, Daniel verfasserin aut Van Tine, Brian A. verfasserin aut Govindan, Ramaswamy verfasserin aut Luo, Jingqin verfasserin aut Lockhart, A. Craig verfasserin aut Wang-Gillam, Andrea verfasserin aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 87(2020), 3 vom: 06. Nov., Seite 337-347 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:87 year:2020 number:3 day:06 month:11 pages:337-347 https://dx.doi.org/10.1007/s00280-020-04183-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE 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_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 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_2118 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_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 44.40 ASE 44.38 ASE AR 87 2020 3 06 11 337-347
spelling	10.1007/s00280-020-04183-0 doi (DE-627)SPR043209629 (DE-599)SPRs00280-020-04183-0-e (SPR)s00280-020-04183-0-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Park, Haeseong verfasserin aut A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213 Williams, Kerry verfasserin aut Trikalinos, Nikolaos A. verfasserin aut Larson, Sarah verfasserin aut Tan, Benjamin verfasserin aut Waqar, Saiama verfasserin aut Suresh, Rama verfasserin aut Morgensztern, Daniel verfasserin aut Van Tine, Brian A. verfasserin aut Govindan, Ramaswamy verfasserin aut Luo, Jingqin verfasserin aut Lockhart, A. Craig verfasserin aut Wang-Gillam, Andrea verfasserin aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 87(2020), 3 vom: 06. Nov., Seite 337-347 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:87 year:2020 number:3 day:06 month:11 pages:337-347 https://dx.doi.org/10.1007/s00280-020-04183-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE 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_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 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_2118 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_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 44.40 ASE 44.38 ASE AR 87 2020 3 06 11 337-347
allfields_unstemmed	10.1007/s00280-020-04183-0 doi (DE-627)SPR043209629 (DE-599)SPRs00280-020-04183-0-e (SPR)s00280-020-04183-0-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Park, Haeseong verfasserin aut A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213 Williams, Kerry verfasserin aut Trikalinos, Nikolaos A. verfasserin aut Larson, Sarah verfasserin aut Tan, Benjamin verfasserin aut Waqar, Saiama verfasserin aut Suresh, Rama verfasserin aut Morgensztern, Daniel verfasserin aut Van Tine, Brian A. verfasserin aut Govindan, Ramaswamy verfasserin aut Luo, Jingqin verfasserin aut Lockhart, A. Craig verfasserin aut Wang-Gillam, Andrea verfasserin aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 87(2020), 3 vom: 06. Nov., Seite 337-347 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:87 year:2020 number:3 day:06 month:11 pages:337-347 https://dx.doi.org/10.1007/s00280-020-04183-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE 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_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 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_2118 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_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 44.40 ASE 44.38 ASE AR 87 2020 3 06 11 337-347
allfieldsGer	10.1007/s00280-020-04183-0 doi (DE-627)SPR043209629 (DE-599)SPRs00280-020-04183-0-e (SPR)s00280-020-04183-0-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Park, Haeseong verfasserin aut A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213 Williams, Kerry verfasserin aut Trikalinos, Nikolaos A. verfasserin aut Larson, Sarah verfasserin aut Tan, Benjamin verfasserin aut Waqar, Saiama verfasserin aut Suresh, Rama verfasserin aut Morgensztern, Daniel verfasserin aut Van Tine, Brian A. verfasserin aut Govindan, Ramaswamy verfasserin aut Luo, Jingqin verfasserin aut Lockhart, A. Craig verfasserin aut Wang-Gillam, Andrea verfasserin aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 87(2020), 3 vom: 06. Nov., Seite 337-347 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:87 year:2020 number:3 day:06 month:11 pages:337-347 https://dx.doi.org/10.1007/s00280-020-04183-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE 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_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 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_2118 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_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 44.40 ASE 44.38 ASE AR 87 2020 3 06 11 337-347
allfieldsSound	10.1007/s00280-020-04183-0 doi (DE-627)SPR043209629 (DE-599)SPRs00280-020-04183-0-e (SPR)s00280-020-04183-0-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Park, Haeseong verfasserin aut A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213 Williams, Kerry verfasserin aut Trikalinos, Nikolaos A. verfasserin aut Larson, Sarah verfasserin aut Tan, Benjamin verfasserin aut Waqar, Saiama verfasserin aut Suresh, Rama verfasserin aut Morgensztern, Daniel verfasserin aut Van Tine, Brian A. verfasserin aut Govindan, Ramaswamy verfasserin aut Luo, Jingqin verfasserin aut Lockhart, A. Craig verfasserin aut Wang-Gillam, Andrea verfasserin aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 87(2020), 3 vom: 06. Nov., Seite 337-347 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:87 year:2020 number:3 day:06 month:11 pages:337-347 https://dx.doi.org/10.1007/s00280-020-04183-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE 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_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 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_2118 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_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 44.40 ASE 44.38 ASE AR 87 2020 3 06 11 337-347
language	English
source	Enthalten in Cancer chemotherapy and pharmacology 87(2020), 3 vom: 06. Nov., Seite 337-347 volume:87 year:2020 number:3 day:06 month:11 pages:337-347
sourceStr	Enthalten in Cancer chemotherapy and pharmacology 87(2020), 3 vom: 06. Nov., Seite 337-347 volume:87 year:2020 number:3 day:06 month:11 pages:337-347
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	mTOR inhibitor EGFR inhibitor Phase 1 study
dewey-raw	610
isfreeaccess_bool	false
container_title	Cancer chemotherapy and pharmacology
authorswithroles_txt_mv	Park, Haeseong @@aut@@ Williams, Kerry @@aut@@ Trikalinos, Nikolaos A. @@aut@@ Larson, Sarah @@aut@@ Tan, Benjamin @@aut@@ Waqar, Saiama @@aut@@ Suresh, Rama @@aut@@ Morgensztern, Daniel @@aut@@ Van Tine, Brian A. @@aut@@ Govindan, Ramaswamy @@aut@@ Luo, Jingqin @@aut@@ Lockhart, A. Craig @@aut@@ Wang-Gillam, Andrea @@aut@@
publishDateDaySort_date	2020-11-06T00:00:00Z
hierarchy_top_id	253390435
dewey-sort	3610
id	SPR043209629
language_de	englisch
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We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. 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author	Park, Haeseong
spellingShingle	Park, Haeseong ddc 610 bkl 44.40 bkl 44.38 misc mTOR inhibitor misc EGFR inhibitor misc Phase 1 study A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors
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topic_title	610 ASE 44.40 bkl 44.38 bkl A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors mTOR inhibitor (dpeaa)DE-He213 EGFR inhibitor (dpeaa)DE-He213 Phase 1 study (dpeaa)DE-He213
topic	ddc 610 bkl 44.40 bkl 44.38 misc mTOR inhibitor misc EGFR inhibitor misc Phase 1 study
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hierarchy_parent_title	Cancer chemotherapy and pharmacology
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title	A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors
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title_full	A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors
author_sort	Park, Haeseong
journal	Cancer chemotherapy and pharmacology
journalStr	Cancer chemotherapy and pharmacology
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author_browse	Park, Haeseong Williams, Kerry Trikalinos, Nikolaos A. Larson, Sarah Tan, Benjamin Waqar, Saiama Suresh, Rama Morgensztern, Daniel Van Tine, Brian A. Govindan, Ramaswamy Luo, Jingqin Lockhart, A. Craig Wang-Gillam, Andrea
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title_sort	phase i trial of temsirolimus and erlotinib in patients with refractory solid tumors
title_auth	A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors
abstract	Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263).
abstractGer	Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263).
abstract_unstemmed	Purpose Resistance to treatment with inhibitors of mammalian target of rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). We conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods Standard “3 + 3” design was used for dose escalation. An expansion cohort at RP2D included only patients with squamous histology or mutations relevant to PI3K or EGFR pathway activation. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was then administered weekly. Starting dose levels were 15 mg for temsirolimus and 100 mg for erlotinib. Results Forty-four patients received treatment on this study (28 in dose escalation and 16 in the expansion cohort). The RP2D was temsirolimus 25 mg IV weekly and erlotinib 100 mg orally daily. Two patients experienced DLTs (G3 dehydration and G4 renal failure). The most common drug-related adverse events (all grades) were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. No complete or partial responses were observed. The median duration on this study was 69 days (range 3–770) for escalation and 88 days (range 25–243) for expansion cohorts. Among 11 response-evaluable patients in the expansion cohort, 9 (82%) had stable disease and 2 (18%) had progressive disease. Conclusion The combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263).
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container_issue	3
title_short	A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors
url	https://dx.doi.org/10.1007/s00280-020-04183-0
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author2	Williams, Kerry Trikalinos, Nikolaos A. Larson, Sarah Tan, Benjamin Waqar, Saiama Suresh, Rama Morgensztern, Daniel Van Tine, Brian A. Govindan, Ramaswamy Luo, Jingqin Lockhart, A. Craig Wang-Gillam, Andrea
author2Str	Williams, Kerry Trikalinos, Nikolaos A. Larson, Sarah Tan, Benjamin Waqar, Saiama Suresh, Rama Morgensztern, Daniel Van Tine, Brian A. Govindan, Ramaswamy Luo, Jingqin Lockhart, A. Craig Wang-Gillam, Andrea
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doi_str	10.1007/s00280-020-04183-0
up_date	2024-07-03T17:15:10.588Z
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A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors

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