PMID- 31159765
OWN - NLM
STAT- MEDLINE
DCOM- 20191211
LR  - 20231012
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Jun 3
TI  - 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).
PG  - 533
LID - 10.1186/s12885-019-5753-7 [doi]
LID - 533
AB  - 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.
FAU - Carrato, A
AU  - Carrato A
AUID- ORCID: 0000-0001-7749-8140
AD  - Medical Oncology Department, Hospital Universitario Ramon y Cajal, IRYCIS, 
      CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034, Madrid, 
      Spain. acarrato@telefonica.net.
FAU - Benavides, M
AU  - Benavides M
AD  - Hospital Regional Universitario Virgen de la Victoria, Malaga, Spain.
FAU - Massuti, B
AU  - Massuti B
AD  - Hospital General Universitario de Alicante, Alicante, Spain.
FAU - Ferreiro-Monteagudo, R
AU  - Ferreiro-Monteagudo R
AD  - Medical Oncology Department, Hospital Universitario Ramon y Cajal, IRYCIS, 
      CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034, Madrid, 
      Spain.
FAU - Garcia Alfonso, P
AU  - Garcia Alfonso P
AD  - Hospital Gregorio Maranon, Madrid, Spain.
FAU - Falco, E
AU  - Falco E
AD  - Hospital Son Llatzer, Mallorca, Spain.
FAU - Reboredo, M
AU  - Reboredo M
AD  - Complejo Hospitalario Universitario A Coruna, La Coruna, Spain.
FAU - Cano, T
AU  - Cano T
AD  - Hospital Universitario Reina Sofia, IMIBIC, University of Cordoba, CIBERONC, 
      Instituto de Salud Carlos III, Cordoba, Spain.
FAU - Gallego, J
AU  - Gallego J
AD  - Hospital General Universitario de Elche, Alicante, Spain.
FAU - Vieitez, J M
AU  - Vieitez JM
AD  - Hospital Universitario Central de Asturias, Oviedo, Spain.
FAU - Layos, L
AU  - Layos L
AD  - Hospital Germans Trias i Pujol, ICO, Badalona, Spain.
FAU - Salud, A
AU  - Salud A
AD  - Hospital de Lleida Arnau de Vilanova, Lerida, Spain.
FAU - Polo, E
AU  - Polo E
AD  - Hospital Miguel Servet, Zaragoza, Spain.
FAU - Dotor, E
AU  - Dotor E
AD  - Corporacio Sanitaria Parc Tauli, Barcelona, Spain.
FAU - Duran-Ogalla, G
AU  - Duran-Ogalla G
AD  - Hospital Regional Universitario Virgen de la Victoria, Malaga, Spain.
FAU - Rodriguez-Garrote, M
AU  - Rodriguez-Garrote M
AD  - Medical Oncology Department, Hospital Universitario Ramon y Cajal, IRYCIS, 
      CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034, Madrid, 
      Spain.
FAU - Calvo, A
AU  - Calvo A
AD  - Hospital Gregorio Maranon, Madrid, Spain.
FAU - Grande, E
AU  - Grande E
AD  - Medical Oncology Department, Hospital Universitario Ramon y Cajal, IRYCIS, 
      CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034, Madrid, 
      Spain.
FAU - Aranda, E
AU  - Aranda E
AD  - Hospital Universitario Reina Sofia, IMIBIC, University of Cordoba, CIBERONC, 
      Instituto de Salud Carlos III, Cordoba, Spain.
LA  - eng
GR  - The Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), 
      Madrid, Spain/Bayer Hispania (ES)/
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190603
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 24T2A1DOYB (regorafenib)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Asthenia/etiology
MH  - Colorectal Neoplasms/*drug therapy/mortality
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Follow-Up Studies
MH  - *Frail Elderly
MH  - Humans
MH  - Hypertension/etiology
MH  - Hypophosphatemia/etiology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Phenylurea Compounds/administration & dosage/*adverse effects/*therapeutic use
MH  - Pilot Projects
MH  - Progression-Free Survival
MH  - Pyridines/administration & dosage/*adverse effects/*therapeutic use
MH  - Spain
MH  - Treatment Outcome
PMC - PMC6547483
OTO - NOTNLM
OT  - Colorectal cancer
OT  - Elderly
OT  - First-line
OT  - Frail patients
OT  - Monotherapy
OT  - Regorafenib
COIS- Vieitez has received honoraria for advisory activities from Bayer. Grande has 
      received research fundings from Bayer, Astellas, Pfizer and AstraZeneca. Aranda 
      has received honoraria for advisory role from Amgen, Bayer, Celgene, Merck, Roche 
      and Sanofi. Carrato has received honoraria for advisory activities from Bayer, 
      Pfizer, Merck and Shire. The other authors have stated that they have no 
      conflicts of interest.
EDAT- 2019/06/05 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/06/03
CRDT- 2019/06/05 06:00
PHST- 2018/12/04 00:00 [received]
PHST- 2019/05/27 00:00 [accepted]
PHST- 2019/06/05 06:00 [entrez]
PHST- 2019/06/05 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/03 00:00 [pmc-release]
AID - 10.1186/s12885-019-5753-7 [pii]
AID - 5753 [pii]
AID - 10.1186/s12885-019-5753-7 [doi]
PST - epublish
SO  - BMC Cancer. 2019 Jun 3;19(1):533. doi: 10.1186/s12885-019-5753-7.