Real-world data on the management of pazopanib-induced liver toxicity in routine care of renal cell cancer and soft tissue sarcoma patients

© 2023. The Author(s)..

PURPOSE: Pazopanib is known to cause liver toxicity. A relationship between pazopanib exposure and alanine transaminase elevations has been described in clinical trials. This study investigated the relation between pazopanib exposure and liver toxicity in real-world patients and evaluated the management of pazopanib-induced liver toxicity in routine care.

METHODS: A retrospective observational cohort study was performed in patients treated with pazopanib in whom pazopanib exposure was measured. The percentage of patients with and without liver toxicity during treatment with pazopanib was calculated as well as the average pazopanib exposure in both groups. Furthermore, the management of patients with liver toxicity was evaluated.

RESULTS: Liver toxicity was observed in 25 out of the 133 patients included (19%). Pazopanib exposure was comparable in patients with or without liver toxicity (27.7 mg/L versus 28.1 mg/L). Seven patients permanently discontinued pazopanib after the occurrence of liver toxicity. Of the remaining 18 patients, continuation or restart of pazopanib after liver toxicity was successful in 16 patients and half of these patients were able to safely continue pazopanib at the same dose as prior to liver toxicity for the remaining duration of treatment.

CONCLUSION: Our study did not demonstrate a clear relationship between pazopanib exposure and the occurrence of pazopanib-induced liver toxicity. Half of the patients were able to safely continue or restart pazopanib treatment after liver toxicity and received the same dose as prior to drug withdrawal. Successful interventions to address pazopanib-induced toxicity in the clinic led to an algorithm for the management of pazopanib-induced liver toxicity.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:93

Enthalten in:

Cancer chemotherapy and pharmacology - 93(2024), 4 vom: 21. März, Seite 353-364

Sprache:

Englisch

Beteiligte Personen:

Westerdijk, K [VerfasserIn]
Krens, S D [VerfasserIn]
Steeghs, N [VerfasserIn]
van der Graaf, W T A [VerfasserIn]
Tjwa, E T T L [VerfasserIn]
Westdorp, H [VerfasserIn]
Desar, I M E [VerfasserIn]
van Erp, N P [VerfasserIn]

Links:

Volltext

Themen:

7RN5DR86CK
Drug-induced liver injury
Indazoles
Journal Article
Liver toxicity
Observational Study
Pazopanib
Prednisolone
Pyrimidines
Sulfonamides
Therapeutic drug monitoring

Anmerkungen:

Date Completed 20.03.2024

Date Revised 22.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00280-023-04615-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365950017