Evidence map›Paper›PMID 32274565›Full record

ArticleCancer chemotherapy and pharmacology2020

Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.

L H Mammatas, A S Zandvliet, M Rovithi, R J Honeywell, E L Swart, G J Peters, C W Menke-van der Houven van Oordt, H M W Verheul

Open access · hybridAbstract readClinical Trial, Phase I
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 21% of its field
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

8 citing papers in PubMed, 14 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

L H MammatasDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
A S ZandvlietDepartment of Clinical Pharmacology and Pharmacy, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
M RovithiDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
R J HoneywellDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
E L SwartDepartment of Clinical Pharmacology and Pharmacy, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
G J PetersDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
C W Menke-van der Houven van OordtDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.
H M W VerheulDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands. Henk.verheul@radboudumc.nl.
Amsterdam University Medical Centers · NLGdańsk Medical University · PLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background(Pre)clinical evidence is accumulating that intermittent exposure to increased doses of protein kinase inhibitors may improve their treatment benefit. In this phase I trial, the safety of high-dose, pulsatile sorafenib was studied. PATIENTS AND

methodsHigh-dose sorafenib was administered once weekly in exposure escalation cohorts according to a 3 + 3 design. Drug monitoring was performed in weeks 1-3 and doses were adjusted to achieve a predefined target plasma area under the curve (AUC)(0-12 h). The effect of low gastric pH on improving sorafenib exposure was investigated by intake of the acidic beverage cola.

resultsSeventeen patients with advanced malignancies without standard treatment options were included. Once weekly, high-dose sorafenib exposure was escalated up to a target AUC(0-12 h) of 125-150 mg/L/h, achieving a twofold higher C

conclusionTreatment with high-dose, once weekly sorafenib administration resulted in dose-limiting toxicity precluding dose escalation above the exposure cohort of 125-150 mg/L/h. Drug monitoring was a successful strategy to pursue a target exposure.

Indexed as

SorafenibArea Under CurveDose-Response Relationship, DrugDrug Administration ScheduleDrug MonitoringDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedNeoplasmsProtein Kinase InhibitorsPulse Therapy, DrugTreatment OutcomeProtein Kinase InhibitorsSorafenibColaDrug monitoringHigh dosePhase I clinical trialPulsatileSorafenib

Identifiers

PMID32274565
PMCPMC7188706
OpenAlexW3015768571

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Registered trials

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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.