First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Carrato, Alfredo; Benavides, Manuel; Massuti, B.; Ferreiro-Monteagudo, R.; Garcia Alfonso, Pilar; Falcó, Esther; Reboredo, M.; Cano, T.; Gallego, Javier; Vieitez, J. M.; Layos, L.; Salud, Antonia; Polo, E.; Dotor, Emma; Duran-Ogalla, G.; Rodriguez-Garrote, M.; Calvo, Aitana; Grande, E.; Aranda, Enrique

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

BackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal c...

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Autores:	Carrato, Alfredo, Benavides, Manuel, Massuti, B., Ferreiro-Monteagudo, R., Garcia Alfonso, Pilar, Falcó, Esther, Reboredo, M., Cano, T., Gallego, Javier, Vieitez, J. M., Layos, L., Salud, Antonia, Polo, E., Dotor, Emma, Duran-Ogalla, G., Rodriguez-Garrote, M., Calvo, Aitana, Grande, E., Aranda, Enrique
Tipo de recurso:	artículo
Fecha de publicación:	2019
País:	España
Institución:	Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:	Docusalut
Idioma:	inglés
OAI Identifier:	oai:docusalut.com:20.500.13003/16364
Acceso en línea:	https://hdl.handle.net/20.500.13003/16364
Access Level:	acceso abierto
Palabra clave:	Humans Progression-Free Survival Asthenia Aged Aged, 80 and over Hypertension Middle Aged Male Neoplasm Metastasis Pilot Projects Female Pyridines Colorectal Neoplasms Treatment Outcome Phenylurea Compounds Hypophosphatemia Spain Dose-Response Relationship, Drug Frail Elderly Follow-Up Studies Administration, Oral Anciano Frágil Hipofosfatemia Supervivencia sin Progresión Resultado del Tratamiento Neoplasias Colorrectales Femenino Metástasis de la Neoplasia Masculino Estudios de Seguimiento Administración Oral Hipertensión Piridinas Proyectos Piloto Relación Dosis-Respuesta a Droga Humanos Persona de Mediana Edad Astenia Anciano Anciano de 80 o más Años Compuestos de Fenilurea España Regorafenib Colorectal cancer Monotherapy First-line Frail patients Elderly

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spelling	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)Carrato, AlfredoBenavides, ManuelMassuti, B.Ferreiro-Monteagudo, R.Garcia Alfonso, PilarFalcó, EstherReboredo, M.Cano, T.Gallego, JavierVieitez, J. M.Layos, L.Salud, AntoniaPolo, E.Dotor, EmmaDuran-Ogalla, G.Rodriguez-Garrote, M.Calvo, AitanaGrande, E.Aranda, EnriqueHumansProgression-Free SurvivalAstheniaAgedAged, 80 and overHypertensionMiddle AgedMaleNeoplasm MetastasisPilot ProjectsFemalePyridinesColorectal NeoplasmsTreatment OutcomePhenylurea CompoundsHypophosphatemiaSpainDose-Response Relationship, DrugFrail ElderlyFollow-Up StudiesAdministration, OralAged, 80 and overAnciano FrágilHipofosfatemiaSupervivencia sin ProgresiónResultado del TratamientoNeoplasias ColorrectalesFemeninoMetástasis de la NeoplasiaMasculinoEstudios de SeguimientoAdministración OralHipertensiónPiridinasProyectos PilotoRelación Dosis-Respuesta a DrogaHumanosPersona de Mediana EdadAsteniaAncianoAnciano de 80 o más AñosCompuestos de FenilureaEspañaRegorafenibColorectal cancerMonotherapyFirst-lineFrail patientsElderlyBackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6months. Treatment consisted of 28-daycycles of orally administered regorafenib 160mg/day (3 weeks followed by 1 week rest).ResultsForty-seven patients were included in the study. Median age was 81years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6months (95%CI 2.7-8.4). Median overall survival (OS) was 16months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).ConclusionsThe study did not meet the pre-specified boundary of 55% PFS rate at 6months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.Trial registrationThis trial was prospectively registered at EudraCT (2013-000236-94). Date of trial registration: April 9th, 2013.BMC20192019-06-0320192019-06-03research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/16364reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/163642026-06-22T12:44:07Z
dc.title.none.fl_str_mv	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
title	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
spellingShingle	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) Carrato, Alfredo Humans Progression-Free Survival Asthenia Aged Aged, 80 and over Hypertension Middle Aged Male Neoplasm Metastasis Pilot Projects Female Pyridines Colorectal Neoplasms Treatment Outcome Phenylurea Compounds Hypophosphatemia Spain Dose-Response Relationship, Drug Frail Elderly Follow-Up Studies Administration, Oral Aged, 80 and over Anciano Frágil Hipofosfatemia Supervivencia sin Progresión Resultado del Tratamiento Neoplasias Colorrectales Femenino Metástasis de la Neoplasia Masculino Estudios de Seguimiento Administración Oral Hipertensión Piridinas Proyectos Piloto Relación Dosis-Respuesta a Droga Humanos Persona de Mediana Edad Astenia Anciano Anciano de 80 o más Años Compuestos de Fenilurea España Regorafenib Colorectal cancer Monotherapy First-line Frail patients Elderly
title_short	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
title_full	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
title_fullStr	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
title_full_unstemmed	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
title_sort	First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
dc.creator.none.fl_str_mv	Carrato, Alfredo Benavides, Manuel Massuti, B. Ferreiro-Monteagudo, R. Garcia Alfonso, Pilar Falcó, Esther Reboredo, M. Cano, T. Gallego, Javier Vieitez, J. M. Layos, L. Salud, Antonia Polo, E. Dotor, Emma Duran-Ogalla, G. Rodriguez-Garrote, M. Calvo, Aitana Grande, E. Aranda, Enrique
author	Carrato, Alfredo
author_facet	Carrato, Alfredo Benavides, Manuel Massuti, B. Ferreiro-Monteagudo, R. Garcia Alfonso, Pilar Falcó, Esther Reboredo, M. Cano, T. Gallego, Javier Vieitez, J. M. Layos, L. Salud, Antonia Polo, E. Dotor, Emma Duran-Ogalla, G. Rodriguez-Garrote, M. Calvo, Aitana Grande, E. Aranda, Enrique
author_role	author
author2	Benavides, Manuel Massuti, B. Ferreiro-Monteagudo, R. Garcia Alfonso, Pilar Falcó, Esther Reboredo, M. Cano, T. Gallego, Javier Vieitez, J. M. Layos, L. Salud, Antonia Polo, E. Dotor, Emma Duran-Ogalla, G. Rodriguez-Garrote, M. Calvo, Aitana Grande, E. Aranda, Enrique
author2_role	author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Humans Progression-Free Survival Asthenia Aged Aged, 80 and over Hypertension Middle Aged Male Neoplasm Metastasis Pilot Projects Female Pyridines Colorectal Neoplasms Treatment Outcome Phenylurea Compounds Hypophosphatemia Spain Dose-Response Relationship, Drug Frail Elderly Follow-Up Studies Administration, Oral Aged, 80 and over Anciano Frágil Hipofosfatemia Supervivencia sin Progresión Resultado del Tratamiento Neoplasias Colorrectales Femenino Metástasis de la Neoplasia Masculino Estudios de Seguimiento Administración Oral Hipertensión Piridinas Proyectos Piloto Relación Dosis-Respuesta a Droga Humanos Persona de Mediana Edad Astenia Anciano Anciano de 80 o más Años Compuestos de Fenilurea España Regorafenib Colorectal cancer Monotherapy First-line Frail patients Elderly
topic	Humans Progression-Free Survival Asthenia Aged Aged, 80 and over Hypertension Middle Aged Male Neoplasm Metastasis Pilot Projects Female Pyridines Colorectal Neoplasms Treatment Outcome Phenylurea Compounds Hypophosphatemia Spain Dose-Response Relationship, Drug Frail Elderly Follow-Up Studies Administration, Oral Aged, 80 and over Anciano Frágil Hipofosfatemia Supervivencia sin Progresión Resultado del Tratamiento Neoplasias Colorrectales Femenino Metástasis de la Neoplasia Masculino Estudios de Seguimiento Administración Oral Hipertensión Piridinas Proyectos Piloto Relación Dosis-Respuesta a Droga Humanos Persona de Mediana Edad Astenia Anciano Anciano de 80 o más Años Compuestos de Fenilurea España Regorafenib Colorectal cancer Monotherapy First-line Frail patients Elderly
description	BackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6months. Treatment consisted of 28-daycycles of orally administered regorafenib 160mg/day (3 weeks followed by 1 week rest).ResultsForty-seven patients were included in the study. Median age was 81years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6months (95%CI 2.7-8.4). Median overall survival (OS) was 16months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).ConclusionsThe study did not meet the pre-specified boundary of 55% PFS rate at 6months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.Trial registrationThis trial was prospectively registered at EudraCT (2013-000236-94). Date of trial registration: April 9th, 2013.
publishDate	2019
dc.date.none.fl_str_mv	2019 2019-06-03 2019 2019-06-03
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.13003/16364
url	https://hdl.handle.net/20.500.13003/16364
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BMC
publisher.none.fl_str_mv	BMC
dc.source.none.fl_str_mv	reponame:Docusalut instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str	Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str	Docusalut
collection	Docusalut
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First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

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