Effect of sorafenib starting dose and dose intensity on survival in patients with hepatocellular carcinoma: Results from a Canadian Multicenter Database.
discontinuation rate
dose intensity
hepatocellular carcinoma
sorafenib
starting dose
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
03
2020
revised:
21
05
2020
accepted:
26
05
2020
pubmed:
13
6
2020
medline:
14
5
2021
entrez:
13
6
2020
Statut:
ppublish
Résumé
Sorafenib has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC), however, full dose can be difficult to tolerate. The aim of this study was to determine whether sorafenib starting dose and mean dose intensity affect survival. Patients treated with sorafenib for HCC from January 2008 to July 2016 in several Canadian provinces were included and retrospectively analyzed. The primary end point was overall survival (OS) of patients starting on sorafenib full dose compared to reduced dose. Secondary analysis compared OS with different mean dose-intensity groups. Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. A propensity score analysis was performed to account for treatment bias and confounding. Of 681 patients included, sorafenib was started at full dose in 289 patients (42%). Median survival for starting full and reduced dose was 9.4 months and 8.9 months (P = .15) respectively. After propensity score matching and adjusting for potential confounders there was still no difference in survival (HR 0.8, 95% CI, 0.61-1.06, P = .12). Almost half of the patients (45%) received a dose intensity < 50%. Median survival for mean dose intensity > 75%, 50%-75%, and < 50% were 9.5 months, 12.9 months, and 7.1 months (P = .005) respectively. In multivariable models, starting dose(HR 1.16, 95% CI 0.93-1.44, P = .180) and mean dose intensity were not associated with survival. Starting HCC patients on a reduced dose of sorafenib compared to full dose may not compromise survival. Mean dose-intensity of sorafenib may also not affect survival.
Sections du résumé
BACKGROUND
Sorafenib has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC), however, full dose can be difficult to tolerate. The aim of this study was to determine whether sorafenib starting dose and mean dose intensity affect survival.
METHODS
Patients treated with sorafenib for HCC from January 2008 to July 2016 in several Canadian provinces were included and retrospectively analyzed. The primary end point was overall survival (OS) of patients starting on sorafenib full dose compared to reduced dose. Secondary analysis compared OS with different mean dose-intensity groups. Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. A propensity score analysis was performed to account for treatment bias and confounding.
RESULTS
Of 681 patients included, sorafenib was started at full dose in 289 patients (42%). Median survival for starting full and reduced dose was 9.4 months and 8.9 months (P = .15) respectively. After propensity score matching and adjusting for potential confounders there was still no difference in survival (HR 0.8, 95% CI, 0.61-1.06, P = .12). Almost half of the patients (45%) received a dose intensity < 50%. Median survival for mean dose intensity > 75%, 50%-75%, and < 50% were 9.5 months, 12.9 months, and 7.1 months (P = .005) respectively. In multivariable models, starting dose(HR 1.16, 95% CI 0.93-1.44, P = .180) and mean dose intensity were not associated with survival.
CONCLUSIONS
Starting HCC patients on a reduced dose of sorafenib compared to full dose may not compromise survival. Mean dose-intensity of sorafenib may also not affect survival.
Identifiants
pubmed: 32529797
doi: 10.1002/cam4.3228
pmc: PMC7367626
doi:
Substances chimiques
Antineoplastic Agents
0
Sorafenib
9ZOQ3TZI87
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
4918-4928Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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