Hyperthermic intraperitoneal chemotherapy in colorectal cancer.
Humans
Colorectal Neoplasms
/ therapy
Male
Female
Hyperthermic Intraperitoneal Chemotherapy
Middle Aged
Peritoneal Neoplasms
/ secondary
Mitomycin
/ administration & dosage
Aged
Oxaliplatin
/ administration & dosage
Cytoreduction Surgical Procedures
Retrospective Studies
Adult
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Propensity Score
Disease-Free Survival
Treatment Outcome
Proportional Hazards Models
Journal
BJS open
ISSN: 2474-9842
Titre abrégé: BJS Open
Pays: England
ID NLM: 101722685
Informations de publication
Date de publication:
08 May 2024
08 May 2024
Historique:
received:
24
11
2022
revised:
13
12
2023
accepted:
13
12
2023
medline:
10
5
2024
pubmed:
10
5
2024
entrez:
9
5
2024
Statut:
ppublish
Résumé
This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.
Sections du résumé
BACKGROUND
BACKGROUND
This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients.
PATIENTS AND METHODS
METHODS
Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed.
RESULTS
RESULTS
Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period.
CONCLUSIONS
CONCLUSIONS
Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.
Identifiants
pubmed: 38722737
pii: 7667694
doi: 10.1093/bjsopen/zrae017
pii:
doi:
Substances chimiques
Mitomycin
50SG953SK6
Oxaliplatin
04ZR38536J
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Kjersti Flatmark
(K)
Wilhelm Graf
(W)
Heikki Takala
(H)
Andrew M Lowy
(AM)
Terence Chua
(T)
Joerg Pelz
(J)
Dario Baratti
(D)
Joel M Baumgartner
(JM)
Richard Berri
(R)
Pedro Bretcha-Boix
(P)
Marcello Deraco
(M)
Guillermo Flores-Ayala
(G)
Alberto Gomez-Portilla
(A)
Santiago González-Moreno
(S)
Martin Goodman
(M)
Evgenia Halkia
(E)
Shigeki Kusamura
(S)
Mecker Moller
(M)
Guillaume Passot
(G)
Marc Pocard
(M)
George Salti
(G)
Armando Sardi
(A)
Maheswari Senthil
(M)
John Spilioitis
(J)
Juan Torres-Melero
(J)
Kiran Turaga
(K)
Jean-Marc Bereder
(JM)
Jean-Louis Bernard
(JL)
Naoual Bakrin
(N)
Sébastien Carrère
(S)
Julien Coget
(J)
Eddy Cotte
(E)
Olivier Facy
(O)
Maximiliano Gelli
(M)
François-Noël Gilly
(FN)
Pablo Ortega-Deballon
(P)
Guillaume Passot
(G)
Patrick Rat
(P)
Pascal Rousset
(P)
Emilie Thibaudeau
(E)
Delphine Vaudoyer
(D)
Informations de copyright
© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.