PMID- 37301718
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20231204
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 189
DP  - 2023 Aug
TI  - Adverse events during first-line treatments for mCRC: The Toxicity over Time 
      (ToxT) analysis of three randomised trials.
PG  - 112910
LID - S0959-8049(23)00229-0 [pii]
LID - 10.1016/j.ejca.2023.05.001 [doi]
AB  - BACKGROUND: In clinical trials, the assessment of safety is traditionally focused 
      on the overall rate of high-grade and serious adverse events (AEs). A new 
      approach to AEs evaluation, taking into account chronic low-grade AEs, single 
      patient's perspective, and time-related information, such as ToxT analysis, 
      should be considered especially for less intense but potentially long-lasting 
      treatments, such as maintenance strategies in metastatic colorectal cancer 
      (mCRC). PATIENTS AND METHODS: We applied ToxT (Toxicity over Time) evaluation to 
      a large cohort of mCRC patients enroled in randomised TRIBE, TRIBE2, and 
      VALENTINO studies, in order to longitudinally describe AEs throughout the whole 
      treatment duration and to compare AEs evolution over cycles between induction and 
      maintenance strategies, providing numerical and graphical results overall and per 
      single patient. After 4-6 months of combination therapy, 
      5-fluorouracil/leucovorin (5-FU/LV) + bevacizumab or panitumumab was recommended 
      in all studies except for the 50% of patients in the VALENTINO trial who received 
      panitumumab alone. RESULTS: Out of 1400 patients included, 42% received FOLFOXIRI 
      (5-FU/LV, oxaliplatin, and irinotecan)/bevacizumab, 18% FOLFIRI/bevacizumab, 24% 
      FOLFOX/bevacizumab, 16% FOLFOX/panitumumab. Mean grade of general and 
      haematological AEs was higher in the first cycles, then progressively decreasing 
      after the end of induction (p < 0.001), and always remaining at the highest 
      levels with FOLFOXIRI/bevacizumab (p < 0.001). Neurotoxicity became more frequent 
      over the cycles with late high-grade episodes (p < 0.001), while the incidence 
      but not the grade of hand-and-foot syndrome gradually increased (p = 0.91). 
      Anti-VEGF-related AEs were more severe in the first cycles, then setting over at 
      low levels (p = 0.03), while anti-EGFR-related AEs still affected patients during 
      maintenance. CONCLUSIONS: Most of chemotherapy-related AEs (except for HFS and 
      neuropathy) reach the highest level in the first cycles, then decrease, probably 
      due to their active clinical management. Transition to maintenance allows relief 
      from most AEs, especially with bevacizumab-based regimens, while 
      anti-EGFR-related AEs may persist.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Boccaccino, Alessandra
AU  - Boccaccino A
AD  - Unit of Oncology, University Hospital of Pisa, Pisa, Italy and Department of 
      Translational Research and New Technologies in Medicine and Surgery, University 
      of Pisa, Via Roma 67, 56126, Pisa, Italy.
FAU - Rossini, Daniele
AU  - Rossini D
AD  - Unit of Oncology, University Hospital of Pisa, Pisa, Italy and Department of 
      Translational Research and New Technologies in Medicine and Surgery, University 
      of Pisa, Via Roma 67, 56126, Pisa, Italy.
FAU - Raimondi, Alessandra
AU  - Raimondi A
AD  - Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via 
      Giacomo Venezian 1, 20133 Milan, Italy.
FAU - Carullo, Martina
AU  - Carullo M
AD  - Unit of Oncology, University Hospital of Pisa, Pisa, Italy and Department of 
      Translational Research and New Technologies in Medicine and Surgery, University 
      of Pisa, Via Roma 67, 56126, Pisa, Italy.
FAU - Lonardi, Sara
AU  - Lonardi S
AD  - Medical Oncology 3, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
FAU - Morano, Federica
AU  - Morano F
AD  - Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via 
      Giacomo Venezian 1, 20133 Milan, Italy.
FAU - Santini, Daniele
AU  - Santini D
AD  - Oncologia Medica Universita Campus Biomedico, Rome, Italy and UOC Oncologia 
      Universitaria, Sapienza University of Rome, Polo Pontino, Italy.
FAU - Tomasello, Gianluca
AU  - Tomasello G
AD  - Oncologia Medica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via 
      Francesco Sforza 28, 20122 Milano, Italy.
FAU - Niger, Monica
AU  - Niger M
AD  - Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via 
      Giacomo Venezian 1, 20133 Milan, Italy.
FAU - Zaniboni, Alberto
AU  - Zaniboni A
AD  - Medical Oncology, Fondazione Poliambulanza, Brescia, Italy.
FAU - Daniel, Francesca
AU  - Daniel F
AD  - Medical Oncology 3, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
FAU - Bustreo, Sara
AU  - Bustreo S
AD  - S.C. Oncologia 1 U, A.O.U. Citta della Salute e della Scienza di Torino, Presidio 
      Molinette, Italy.
FAU - Procaccio, Letizia
AU  - Procaccio L
AD  - Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, 
      Italy and Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, 
      Italy.
FAU - Clavarezza, Matteo
AU  - Clavarezza M
AD  - Oncology Unit Galliera Hospital, Genoa, Italy.
FAU - Cupini, Samanta
AU  - Cupini S
AD  - Department of Oncology, Division of Medical Oncology, Azienda Toscana Nord Ovest, 
      Livorno, Italy.
FAU - Libertini, Michela
AU  - Libertini M
AD  - Medical Oncology, Fondazione Poliambulanza, Brescia, Italy.
FAU - Palermo, Federica
AU  - Palermo F
AD  - Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via 
      Giacomo Venezian 1, 20133 Milan, Italy.
FAU - Pietrantonio, Filippo
AU  - Pietrantonio F
AD  - Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via 
      Giacomo Venezian 1, 20133 Milan, Italy.
FAU - Cremolini, Chiara
AU  - Cremolini C
AD  - Unit of Oncology, University Hospital of Pisa, Pisa, Italy and Department of 
      Translational Research and New Technologies in Medicine and Surgery, University 
      of Pisa, Via Roma 67, 56126, Pisa, Italy. Electronic address: 
      chiaracremolini@gmail.com.
LA  - eng
PT  - Comment
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230506
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 6A901E312A (Panitumumab)
RN  - XT3Z54Z28A (Camptothecin)
RN  - U3P01618RT (Fluorouracil)
RN  - Q573I9DVLP (Leucovorin)
SB  - IM
CON - Lancet Haematol. 2020 Jun;7(6):e490-e497. PMID: 32470440
MH  - Humans
MH  - Bevacizumab
MH  - *Colorectal Neoplasms/drug therapy/pathology
MH  - Panitumumab/therapeutic use
MH  - Camptothecin
MH  - *Colonic Neoplasms/drug therapy
MH  - *Rectal Neoplasms/drug therapy
MH  - Fluorouracil
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Leucovorin
OTO - NOTNLM
OT  - Adverse events
OT  - FOLFOXIRI
OT  - Metastatic colorectal cancer
OT  - Toxicity over Time (ToxT)
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: AR: Honoraria for speaker bureau for Servier and Elma Academy. FM: 
      Honoraria from Servier, Pierre-Fabre and Lilly; Research grant from Incyte.GT: 
      Payment or honoraria for lectures, presentations, speakers bureaus, manuscript 
      writing or educational events from Eli Lilly, Novartis, Amgen, Roche, Merck; 
      Participation on a Data Safety Monitoring Board or Advisory Board: Eli Lilly, 
      Amgen, Roche. MN: Travel expenses from Celgene and AstraZeneca; Speaker 
      honorarium from Accademia della Medicina and Incyte; Honoraria from 
      Sandoz, Medpoint SRL and Servier for editorial collaboration; Consultant 
      honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, 
      Astrazeneca and Taiho. AZ: Speaker Bureau for Amgen, Merck-Serono, 
      Servier, Pierre-Fabre. FP: Honoraria from Amgen, Bayer, Servier, Merck-Serono, 
      Lilly, MSD, Organon, BMS, Astrazeneca, Pierre-Fabre; Research grants from 
      Bristol-Myers Squibb, AstraZeneca, Agenus and Incyte. CC: Honoraria from Amgen, 
      Bayer, Merck, Roche and Servier; Consulting or advisory role: Amgen, Bayer, MSD, 
      Roche; Speakers' Bureau: Servier; Research funding: Bayer, Merck, Servier; Travel 
      accommodations and expenses: Roche and Servier. All the other authors have 
      declared no conflicts of interest.
EDAT- 2023/06/11 01:06
MHDA- 2023/07/17 06:42
CRDT- 2023/06/10 22:00
PHST- 2023/02/22 00:00 [received]
PHST- 2023/04/25 00:00 [revised]
PHST- 2023/05/01 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/06/11 01:06 [pubmed]
PHST- 2023/06/10 22:00 [entrez]
AID - S0959-8049(23)00229-0 [pii]
AID - 10.1016/j.ejca.2023.05.001 [doi]
PST - ppublish
SO  - Eur J Cancer. 2023 Aug;189:112910. doi: 10.1016/j.ejca.2023.05.001. Epub 2023 May 
      6.