PMID- 31573612
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 30
IP  - 12
DP  - 2019 Dec 1
TI  - Impact of age and gender on the safety and efficacy of chemotherapy plus 
      bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and 
      TRIBE2 studies.
PG  - 1969-1977
LID - S0923-7534(20)32558-8 [pii]
LID - 10.1093/annonc/mdz403 [doi]
AB  - BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic 
      colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet 
      (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit 
      from the triplet at the price of an increased incidence of chemotherapy-related 
      adverse events (AEs). In both trials, males and females aged between 18 and 70 
      years with ECOG PS </=2 and between 71 and 75 years with ECOG PS = 0 were eligible. 
      We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab 
      according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to 
      age (<70 versus 70-75 years) and gender were carried out for overall response 
      rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 
      patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) 
      were males and 494 (42%) females. There was no evidence of interaction between 
      age or gender and the benefit provided by the intensification of the upfront 
      chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 
      AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs 
      (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, 
      in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia 
      occurred in 27% and 16% of elderly patients, respectively, while females reported 
      high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The 
      improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus 
      doublets/bevacizumab are independent of gender and age, with a similar relative 
      increase in AEs among elderly patients and females. Initial dose reductions and 
      possibly primary G-CSF prophylaxis should be recommended for patients between 70 
      and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of 
      antiemetic prophylaxis should be considered among females.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      European Society for Medical Oncology. All rights reserved. For permissions, 
      please email: journals.permissions@oup.com.
FAU - Marmorino, F
AU  - Marmorino F
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Rossini, D
AU  - Rossini D
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Lonardi, S
AU  - Lonardi S
AD  - Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto 
      Institute of Oncology - IRCCS, Padova.
FAU - Moretto, R
AU  - Moretto R
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Zucchelli, G
AU  - Zucchelli G
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Aprile, G
AU  - Aprile G
AD  - Department of Oncology, General and University Hospital, Udine; Department of 
      Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza.
FAU - Dell'Aquila, E
AU  - Dell'Aquila E
AD  - Department of Medical Oncology, Campus Biomedico University, Roma.
FAU - Ratti, M
AU  - Ratti M
AD  - Oncology Department, Oncology Unit, ASST of Cremona, Cremona.
FAU - Bergamo, F
AU  - Bergamo F
AD  - Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto 
      Institute of Oncology - IRCCS, Padova.
FAU - Masi, G
AU  - Masi G
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Urbano, F
AU  - Urbano F
AD  - Department of Radiological Science, Oncology and Pathology, Policlinico Umberto 
      I, "Sapienza" University of Rome, Roma.
FAU - Ronzoni, M
AU  - Ronzoni M
AD  - Department of Oncology, Istituto Scientifico San Raffaele IRCSS, Milano.
FAU - Libertini, M
AU  - Libertini M
AD  - Medical Oncology Unit, Poliambulanza Foundation, Brescia.
FAU - Borelli, B
AU  - Borelli B
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Randon, G
AU  - Randon G
AD  - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 
      Milan.
FAU - Buonadonna, A
AU  - Buonadonna A
AD  - Department of Medical Oncology, IRCCS CRO National Cancer Institute, Aviano.
FAU - Allegrini, G
AU  - Allegrini G
AD  - Department of Medical Oncology, Unit of Medical Oncology, Livorno Hospital, 
      Azienda Toscana Nord Ovest, Livorno.
FAU - Pella, N
AU  - Pella N
AD  - Department of Oncology, General and University Hospital, Udine.
FAU - Ricci, V
AU  - Ricci V
AD  - Department of Oncology, S. Croce and Carle Teaching Hospital, Cuneo.
FAU - Boccaccino, A
AU  - Boccaccino A
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Latiano, T P
AU  - Latiano TP
AD  - Oncology Unit, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni 
      Rotondo.
FAU - Cordio, S
AU  - Cordio S
AD  - Medical Oncology Unit, ARNAS Garibaldi Catania, Catania.
FAU - Passardi, A
AU  - Passardi A
AD  - Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la 
      Cura dei Tumori (IRST) IRCCS, Meldola.
FAU - Tamburini, E
AU  - Tamburini E
AD  - Department of Medical Oncology, Card. G. Panico Hospital of Tricase, Tricase.
FAU - Boni, L
AU  - Boni L
AD  - Clinical Trials Coordinating Center, Toscano Cancer Institute, University 
      Hospital Careggi, Firenze, Italy.
FAU - Falcone, A
AU  - Falcone A
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa.
FAU - Cremolini, C
AU  - Cremolini C
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, 
      University of Pisa, Pisa. Electronic address: chiaracremolini@gmail.com.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Organoplatinum Compounds)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
RN  - FOLFOXIRI protocol
RN  - Folfox protocol
SB  - IM
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Bevacizumab/*administration & dosage/adverse effects
MH  - Camptothecin/administration & dosage/adverse effects/*analogs & derivatives
MH  - Colorectal Neoplasms/*drug therapy/epidemiology/pathology
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced/pathology
MH  - Neoplasm Metastasis
MH  - Organoplatinum Compounds/administration & dosage/adverse effects
MH  - Progression-Free Survival
MH  - Sex Characteristics
MH  - Treatment Outcome
MH  - Vomiting/chemically induced/pathology
OTO - NOTNLM
OT  - FOLFOXIRI/bevacizumab
OT  - age
OT  - gender
OT  - metastatic colorectal cancer
EDAT- 2019/10/02 06:00
MHDA- 2020/07/28 06:00
CRDT- 2019/10/02 06:00
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2019/10/02 06:00 [entrez]
AID - S0923-7534(20)32558-8 [pii]
AID - 10.1093/annonc/mdz403 [doi]
PST - ppublish
SO  - Ann Oncol. 2019 Dec 1;30(12):1969-1977. doi: 10.1093/annonc/mdz403.