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, A; Benavides, M; Massuti, B; Ferreiro-Monteagudo, R; Garcia Alfonso, P; Falco, E; Reboredo Lopez, Margarita; Cano, T; Gallego, J; Vieitez, J M; Layos, L; Salud, A; Polo, E; Dotor, E; Duran-Ogalla, G; Rodriguez-Garrote, M; Calvo, A; Grande, E; Aranda, E

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)

BACKGROUND: Treatment 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. METHODS: Frail patients without prior advanced colorec...

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Autores:	Carrato, A, Benavides, M, Massuti, B, Ferreiro-Monteagudo, R, Garcia Alfonso, P, Falco, E, Reboredo Lopez, Margarita, Cano, T, Gallego, J, Vieitez, J M, Layos, L, Salud, A, Polo, E, Dotor, E, Duran-Ogalla, G, Rodriguez-Garrote, M, Calvo, A, Grande, E, Aranda, E
Tipo de recurso:	artículo
Fecha de publicación:	2019
País:	España
Institución:	Servizo Galego de Saúde (SERGAS)
Repositorio:	RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:	oai:runa.sergas.gal:20.500.11940/15934
Acceso en línea:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547483/pdf/12885_2019_Article_5753.pdf https://www.ncbi.nlm.nih.gov/pubmed/31159765 http://hdl.handle.net/20.500.11940/15934
Access Level:	acceso abierto
Palabra clave:	Middle Aged Neoplasm Metastasis Hypophosphatemia Follow-Up Studies Pyridines Humans Treatment Outcome Pilot Projects Asthenia Aged Hypertension Colorectal Neoplasms Phenylurea Compounds resultado del tratamiento hipertensión estudios de seguimiento compuestos de fenilurea mediana edad metástasis neoplásica anciano piridinas proyectos piloto humanos astenia neoplasias colorrectales hipofosfatemia CHUAC

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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, ABenavides, MMassuti, BFerreiro-Monteagudo, RGarcia Alfonso, PFalco, EReboredo Lopez, MargaritaCano, TGallego, JVieitez, J MLayos, LSalud, APolo, EDotor, EDuran-Ogalla, GRodriguez-Garrote, MCalvo, AGrande, EAranda, EMiddle AgedNeoplasm MetastasisHypophosphatemiaFollow-Up StudiesPyridinesHumansTreatment OutcomePilot ProjectsAstheniaAgedHypertensionColorectal NeoplasmsPhenylurea Compoundsresultado del tratamientohipertensiónestudios de seguimientocompuestos de fenilureamediana edadmetástasis neoplásicaancianopiridinasproyectos pilotohumanosastenianeoplasias colorrectaleshipofosfatemiaCHUACBACKGROUND: Treatment 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. METHODS: Frail 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 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (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 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (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%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. 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 REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.2019info:eu-repo/semantics/articlehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547483/pdf/12885_2019_Article_5753.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/31159765http://hdl.handle.net/20.500.11940/15934reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/159342026-06-12T08:40:47Z
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, A Middle Aged Neoplasm Metastasis Hypophosphatemia Follow-Up Studies Pyridines Humans Treatment Outcome Pilot Projects Asthenia Aged Hypertension Colorectal Neoplasms Phenylurea Compounds resultado del tratamiento hipertensión estudios de seguimiento compuestos de fenilurea mediana edad metástasis neoplásica anciano piridinas proyectos piloto humanos astenia neoplasias colorrectales hipofosfatemia CHUAC
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, A Benavides, M Massuti, B Ferreiro-Monteagudo, R Garcia Alfonso, P Falco, E Reboredo Lopez, Margarita Cano, T Gallego, J Vieitez, J M Layos, L Salud, A Polo, E Dotor, E Duran-Ogalla, G Rodriguez-Garrote, M Calvo, A Grande, E Aranda, E
author	Carrato, A
author_facet	Carrato, A Benavides, M Massuti, B Ferreiro-Monteagudo, R Garcia Alfonso, P Falco, E Reboredo Lopez, Margarita Cano, T Gallego, J Vieitez, J M Layos, L Salud, A Polo, E Dotor, E Duran-Ogalla, G Rodriguez-Garrote, M Calvo, A Grande, E Aranda, E
author_role	author
author2	Benavides, M Massuti, B Ferreiro-Monteagudo, R Garcia Alfonso, P Falco, E Reboredo Lopez, Margarita Cano, T Gallego, J Vieitez, J M Layos, L Salud, A Polo, E Dotor, E Duran-Ogalla, G Rodriguez-Garrote, M Calvo, A Grande, E Aranda, E
author2_role	author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Middle Aged Neoplasm Metastasis Hypophosphatemia Follow-Up Studies Pyridines Humans Treatment Outcome Pilot Projects Asthenia Aged Hypertension Colorectal Neoplasms Phenylurea Compounds resultado del tratamiento hipertensión estudios de seguimiento compuestos de fenilurea mediana edad metástasis neoplásica anciano piridinas proyectos piloto humanos astenia neoplasias colorrectales hipofosfatemia CHUAC
topic	Middle Aged Neoplasm Metastasis Hypophosphatemia Follow-Up Studies Pyridines Humans Treatment Outcome Pilot Projects Asthenia Aged Hypertension Colorectal Neoplasms Phenylurea Compounds resultado del tratamiento hipertensión estudios de seguimiento compuestos de fenilurea mediana edad metástasis neoplásica anciano piridinas proyectos piloto humanos astenia neoplasias colorrectales hipofosfatemia CHUAC
description	BACKGROUND: Treatment 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. METHODS: Frail 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 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (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 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (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%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. 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 REGISTRATION: This 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
dc.type.none.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547483/pdf/12885_2019_Article_5753.pdf https://www.ncbi.nlm.nih.gov/pubmed/31159765 http://hdl.handle.net/20.500.11940/15934
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547483/pdf/12885_2019_Article_5753.pdf https://www.ncbi.nlm.nih.gov/pubmed/31159765 http://hdl.handle.net/20.500.11940/15934
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.source.none.fl_str_mv	reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas instname:Servizo Galego de Saúde (SERGAS)
instname_str	Servizo Galego de Saúde (SERGAS)
reponame_str	RUNA. Repositorio da Consellería de Sanidade e Sergas
collection	RUNA. Repositorio da Consellería de Sanidade e Sergas
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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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