Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study

Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-...
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Autor*in:	Sarantopoulos, John [verfasserIn] Mita, Alain C. He, Aiwu Wade, James L. Hsueh, Chung-Tsen Morris, John C. Lockhart, A. Craig Quinn, David I. Hwang, Jimmy Mier, James Zhang, Wenping Wack, Claudine Yin, Jian Clot, Pierre-François Rixe, Olivier

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Cabazitaxel Hepatic impairment Maximum tolerated dose Pharmacokinetics Phase I

Anmerkung:	© The Author(s) 2017

Übergeordnetes Werk:	Enthalten in: Cancer chemotherapy and pharmacology - Berlin : Springer, 1978, 79(2017), 2 vom: 05. Jan., Seite 339-351
Übergeordnetes Werk:	volume:79 ; year:2017 ; number:2 ; day:05 ; month:01 ; pages:339-351

Links:	Volltext

DOI / URN:	10.1007/s00280-016-3210-8

Katalog-ID:	SPR003615227

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100	1		\|a Sarantopoulos, John \|e verfasserin \|4 aut
245	1	0	\|a Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
264		1	\|c 2017
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520			\|a Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data.
650		4	\|a Cabazitaxel \|7 (dpeaa)DE-He213
650		4	\|a Hepatic impairment \|7 (dpeaa)DE-He213
650		4	\|a Maximum tolerated dose \|7 (dpeaa)DE-He213
650		4	\|a Pharmacokinetics \|7 (dpeaa)DE-He213
650		4	\|a Phase I \|7 (dpeaa)DE-He213
700	1		\|a Mita, Alain C. \|4 aut
700	1		\|a He, Aiwu \|4 aut
700	1		\|a Wade, James L. \|4 aut
700	1		\|a Hsueh, Chung-Tsen \|4 aut
700	1		\|a Morris, John C. \|4 aut
700	1		\|a Lockhart, A. Craig \|4 aut
700	1		\|a Quinn, David I. \|4 aut
700	1		\|a Hwang, Jimmy \|4 aut
700	1		\|a Mier, James \|4 aut
700	1		\|a Zhang, Wenping \|4 aut
700	1		\|a Wack, Claudine \|4 aut
700	1		\|a Yin, Jian \|4 aut
700	1		\|a Clot, Pierre-François \|4 aut
700	1		\|a Rixe, Olivier \|4 aut
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allfields	10.1007/s00280-016-3210-8 doi (DE-627)SPR003615227 (SPR)s00280-016-3210-8-e DE-627 ger DE-627 rakwb eng Sarantopoulos, John verfasserin aut Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213 Mita, Alain C. aut He, Aiwu aut Wade, James L. aut Hsueh, Chung-Tsen aut Morris, John C. aut Lockhart, A. Craig aut Quinn, David I. aut Hwang, Jimmy aut Mier, James aut Zhang, Wenping aut Wack, Claudine aut Yin, Jian aut Clot, Pierre-François aut Rixe, Olivier aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 79(2017), 2 vom: 05. Jan., Seite 339-351 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:79 year:2017 number:2 day:05 month:01 pages:339-351 https://dx.doi.org/10.1007/s00280-016-3210-8 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 79 2017 2 05 01 339-351
spelling	10.1007/s00280-016-3210-8 doi (DE-627)SPR003615227 (SPR)s00280-016-3210-8-e DE-627 ger DE-627 rakwb eng Sarantopoulos, John verfasserin aut Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213 Mita, Alain C. aut He, Aiwu aut Wade, James L. aut Hsueh, Chung-Tsen aut Morris, John C. aut Lockhart, A. Craig aut Quinn, David I. aut Hwang, Jimmy aut Mier, James aut Zhang, Wenping aut Wack, Claudine aut Yin, Jian aut Clot, Pierre-François aut Rixe, Olivier aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 79(2017), 2 vom: 05. Jan., Seite 339-351 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:79 year:2017 number:2 day:05 month:01 pages:339-351 https://dx.doi.org/10.1007/s00280-016-3210-8 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 79 2017 2 05 01 339-351
allfields_unstemmed	10.1007/s00280-016-3210-8 doi (DE-627)SPR003615227 (SPR)s00280-016-3210-8-e DE-627 ger DE-627 rakwb eng Sarantopoulos, John verfasserin aut Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213 Mita, Alain C. aut He, Aiwu aut Wade, James L. aut Hsueh, Chung-Tsen aut Morris, John C. aut Lockhart, A. Craig aut Quinn, David I. aut Hwang, Jimmy aut Mier, James aut Zhang, Wenping aut Wack, Claudine aut Yin, Jian aut Clot, Pierre-François aut Rixe, Olivier aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 79(2017), 2 vom: 05. Jan., Seite 339-351 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:79 year:2017 number:2 day:05 month:01 pages:339-351 https://dx.doi.org/10.1007/s00280-016-3210-8 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 79 2017 2 05 01 339-351
allfieldsGer	10.1007/s00280-016-3210-8 doi (DE-627)SPR003615227 (SPR)s00280-016-3210-8-e DE-627 ger DE-627 rakwb eng Sarantopoulos, John verfasserin aut Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213 Mita, Alain C. aut He, Aiwu aut Wade, James L. aut Hsueh, Chung-Tsen aut Morris, John C. aut Lockhart, A. Craig aut Quinn, David I. aut Hwang, Jimmy aut Mier, James aut Zhang, Wenping aut Wack, Claudine aut Yin, Jian aut Clot, Pierre-François aut Rixe, Olivier aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 79(2017), 2 vom: 05. Jan., Seite 339-351 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:79 year:2017 number:2 day:05 month:01 pages:339-351 https://dx.doi.org/10.1007/s00280-016-3210-8 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 79 2017 2 05 01 339-351
allfieldsSound	10.1007/s00280-016-3210-8 doi (DE-627)SPR003615227 (SPR)s00280-016-3210-8-e DE-627 ger DE-627 rakwb eng Sarantopoulos, John verfasserin aut Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213 Mita, Alain C. aut He, Aiwu aut Wade, James L. aut Hsueh, Chung-Tsen aut Morris, John C. aut Lockhart, A. Craig aut Quinn, David I. aut Hwang, Jimmy aut Mier, James aut Zhang, Wenping aut Wack, Claudine aut Yin, Jian aut Clot, Pierre-François aut Rixe, Olivier aut Enthalten in Cancer chemotherapy and pharmacology Berlin : Springer, 1978 79(2017), 2 vom: 05. Jan., Seite 339-351 (DE-627)253390435 (DE-600)1458488-8 1432-0843 nnns volume:79 year:2017 number:2 day:05 month:01 pages:339-351 https://dx.doi.org/10.1007/s00280-016-3210-8 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 79 2017 2 05 01 339-351
language	English
source	Enthalten in Cancer chemotherapy and pharmacology 79(2017), 2 vom: 05. Jan., Seite 339-351 volume:79 year:2017 number:2 day:05 month:01 pages:339-351
sourceStr	Enthalten in Cancer chemotherapy and pharmacology 79(2017), 2 vom: 05. Jan., Seite 339-351 volume:79 year:2017 number:2 day:05 month:01 pages:339-351
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Cabazitaxel Hepatic impairment Maximum tolerated dose Pharmacokinetics Phase I
isfreeaccess_bool	true
container_title	Cancer chemotherapy and pharmacology
authorswithroles_txt_mv	Sarantopoulos, John @@aut@@ Mita, Alain C. @@aut@@ He, Aiwu @@aut@@ Wade, James L. @@aut@@ Hsueh, Chung-Tsen @@aut@@ Morris, John C. @@aut@@ Lockhart, A. Craig @@aut@@ Quinn, David I. @@aut@@ Hwang, Jimmy @@aut@@ Mier, James @@aut@@ Zhang, Wenping @@aut@@ Wack, Claudine @@aut@@ Yin, Jian @@aut@@ Clot, Pierre-François @@aut@@ Rixe, Olivier @@aut@@
publishDateDaySort_date	2017-01-05T00:00:00Z
hierarchy_top_id	253390435
id	SPR003615227
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR003615227</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519190636.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201001s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00280-016-3210-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR003615227</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00280-016-3210-8-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Sarantopoulos, John</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2017</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. 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author	Sarantopoulos, John
spellingShingle	Sarantopoulos, John misc Cabazitaxel misc Hepatic impairment misc Maximum tolerated dose misc Pharmacokinetics misc Phase I Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
authorStr	Sarantopoulos, John
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topic_title	Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study Cabazitaxel (dpeaa)DE-He213 Hepatic impairment (dpeaa)DE-He213 Maximum tolerated dose (dpeaa)DE-He213 Pharmacokinetics (dpeaa)DE-He213 Phase I (dpeaa)DE-He213
topic	misc Cabazitaxel misc Hepatic impairment misc Maximum tolerated dose misc Pharmacokinetics misc Phase I
topic_unstemmed	misc Cabazitaxel misc Hepatic impairment misc Maximum tolerated dose misc Pharmacokinetics misc Phase I
topic_browse	misc Cabazitaxel misc Hepatic impairment misc Maximum tolerated dose misc Pharmacokinetics misc Phase I
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title	Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
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title_full	Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
author_sort	Sarantopoulos, John
journal	Cancer chemotherapy and pharmacology
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container_start_page	339
author_browse	Sarantopoulos, John Mita, Alain C. He, Aiwu Wade, James L. Hsueh, Chung-Tsen Morris, John C. Lockhart, A. Craig Quinn, David I. Hwang, Jimmy Mier, James Zhang, Wenping Wack, Claudine Yin, Jian Clot, Pierre-François Rixe, Olivier
container_volume	79
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author-letter	Sarantopoulos, John
doi_str_mv	10.1007/s00280-016-3210-8
title_sort	safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase i dose-escalation study
title_auth	Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
abstract	Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. © The Author(s) 2017
abstractGer	Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. © The Author(s) 2017
abstract_unstemmed	Purpose Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/$ m^{2} $) than expected (26.4 L/h/$ m^{2} $), but similar in C-2 (23.5 L/h/$ m^{2} $) and C-3 (27.9 L/h/$ m^{2} $). CL/BSA in C-4 was 18.1 L/h/$ m^{2} $. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters. Conclusions Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data. © The Author(s) 2017
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container_issue	2
title_short	Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study
url	https://dx.doi.org/10.1007/s00280-016-3210-8
remote_bool	true
author2	Mita, Alain C. He, Aiwu Wade, James L. Hsueh, Chung-Tsen Morris, John C. Lockhart, A. Craig Quinn, David I. Hwang, Jimmy Mier, James Zhang, Wenping Wack, Claudine Yin, Jian Clot, Pierre-François Rixe, Olivier
author2Str	Mita, Alain C. He, Aiwu Wade, James L. Hsueh, Chung-Tsen Morris, John C. Lockhart, A. Craig Quinn, David I. Hwang, Jimmy Mier, James Zhang, Wenping Wack, Claudine Yin, Jian Clot, Pierre-François Rixe, Olivier
ppnlink	253390435
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1007/s00280-016-3210-8
up_date	2024-07-03T20:40:06.759Z
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This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. Methods Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/$ m^{2} $, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed. Results In C-2, three patients receiving cabazitaxel 25 mg/$ m^{2} $ experienced DLTs; maximum tolerated dose (MTD) was 20 mg/$ m^{2} $. In C-3, two patients receiving 20 mg/$ m^{2} $ experienced DLTs; MTD was 15 mg/$ m^{2} $. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). 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Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study

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