Evidence map›Paper›PMID 39012619›Full record

ArticleClinical pharmacokinetics2024

Evaluating the Clinical Impact and Feasibility of Therapeutic Drug Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort.

Marinda Meertens, Eline L Giraud, Maud B A van der Kleij, Kim Westerdijk, Niels A D Guchelaar, Roos F Bleckman, Amy Rieborn, Alex L T Imholz, Hans-Martin Otten, Annelie Vulink and 14 more

Abstract read
In one paragraph

Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Marinda MeertensDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Eline L GiraudDepartment of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands.
Maud B A van der KleijDepartment of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Kim WesterdijkDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Niels A D GuchelaarDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Roos F BleckmanDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Amy RiebornDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
Alex L T ImholzDepartment of Medical Oncology, Deventer Hospital, Deventer, The Netherlands.
Hans-Martin OttenDepartment of Medical Oncology, Meander Medical Centre, Amersfoort, The Netherlands.
Annelie VulinkDepartment of Medical Oncology, Reinier de Graaf Hospital, Delft, The Netherlands.
Maartje LosDepartment of Medical Oncology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Paul HambergDepartment of Medical Oncology, Franciscus Gasthuis & Vlietland, Schiedam, The Netherlands.
Winette T A van der GraafDepartment of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Hans GelderblomDepartment of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Dirk Jan A R MoesDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
K Esther BroekmanDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Daan J TouwDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
Stijn L W KoolenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Ron H J MathijssenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Alwin D R HuitemaDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Nielka P van ErpDepartment of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands.
Ingrid M E DesarDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Neeltje SteeghsDepartment of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands. n.steeghs@nki.nl.ORCID http://orcid.org/0000-0003-2989-2279
Dutch Pharmacology Oncology Group (DPOG)

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION AND

objectivePazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing.

methodsA TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications.

resultsA total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%).

conclusionTDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients.

Indexed as

Drug MonitoringFeasibility StudiesIndazolesPyrimidinesSarcomaSulfonamidesAdultAgedAged, 80 and overAngiogenesis InhibitorsCohort StudiesFemaleHumansMaleMiddle AgedProgression-Free SurvivalAngiogenesis InhibitorsIndazolespazopanibPyrimidinesSulfonamides

Identifiers

PMID39012619
PMCPMC11271328

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.