First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study.
Chemotherapy toxicity
Metastatic colorectal cancer
Raltitrexed
Survival
Journal
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
02
06
2021
revised:
11
08
2021
accepted:
12
08
2021
pubmed:
3
9
2021
medline:
3
5
2022
entrez:
2
9
2021
Statut:
ppublish
Résumé
In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies. This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. 75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3-4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 - 13.1) and 27.4 months (95% CI 24.1-38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone. In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies.
Sections du résumé
BACKGROUND
In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies.
METHODS
This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start.
RESULTS
75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3-4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 - 13.1) and 27.4 months (95% CI 24.1-38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone.
CONCLUSIONS
In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies.
Identifiants
pubmed: 34470724
pii: S1590-8658(21)00456-4
doi: 10.1016/j.dld.2021.08.009
pii:
doi:
Substances chimiques
Quinazolines
0
Thiophenes
0
Bevacizumab
2S9ZZM9Q9V
raltitrexed
FCB9EGG971
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
684-691Informations de copyright
Copyright © 2021. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Conflict of interest CG has participated in consulting and/or advisory boards for Servier and Sanofi, and has received support for travel to meetings from Amgen. PA has participated in consulting and/or advisory boards for Lilly, Celgene, Shire, Servier, Merck KGaA, Sanofi, Roche Genentech, Pfizer, Pierre Fabre and Amgen. CC has received honoraria from Amgen and Servier, has participated in an advisory board for Servier, and has received support for travel to meetings from Amgen, Bayer, Roche, Mundipharma and Servier. AT reports personal fees from Mylan, personal fees from Merck Serono, personal fees from Amgen, non-financial support from Merck-Serono, non-financial support from Sanofi, and non-financial support from Pfizer outside the submitted work. AP has participated in consulting and/or advisory boards for Servier and Amgen, and has received support for travel meetings from Ipsen. SP has participated in consulting and/or advisory boards for Amgen, Sanofi, Pierre Fabre, Servier, Merck, Roche, has received support for travel to meetings from Amgen, Bayer, and Servier, and has received research grants from Roche, Planet Vegetal. VH has participated in consulting and/or advisory boards for Sanofi, Merck, Amgen, and has received support for travel to meetings from Amgen and Sanofi. JT has participated in consulting and/or advisory boards for Lilly, Celgene, Shire, Servier, Merck KGaA, Sanofi, Roche Genentech, Pfizer, and Amgen. The other authors declare no conflict of interest.