Evidence map›Paper›PMID 36782356›Full record

ArticleCPT: pharmacometrics & systems pharmacology2023

A prognostic baseline blood biomarker and tumor growth kinetics integrated model in paclitaxel/platinum treated advanced non-small cell lung cancer patients.

Francis Williams Ojara, Andrea Henrich, Nicolas Frances, Yomna M Nassar, Wilhelm Huisinga, Niklas Hartung, Kimberly Geiger, Stefan Holdenrieder, Markus Joerger, Charlotte Kloft

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 7 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

10 authors at 5 institutions in 2 countries.

Francis Williams OjaraDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.
Andrea HenrichDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.ORCID 0000-0003-0072-8352
Nicolas FrancesDepartment of Translational Modeling and Simulation, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Yomna M NassarDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.ORCID 0000-0003-0507-7130
Wilhelm HuisingaInstitute of Mathematics, University of Potsdam, Potsdam, Germany.ORCID 0000-0002-5249-3914
Niklas HartungInstitute of Mathematics, University of Potsdam, Potsdam, Germany.ORCID 0000-0002-4000-6525
Kimberly GeigerMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University of Munich, Munich, Germany.
Stefan HoldenriederMunich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University of Munich, Munich, Germany.
Markus JoergerDepartment of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Charlotte KloftDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.
Freie Universität Berlin · DEDeutsches Herzzentrum München · DEUniversity of Potsdam · DERoche (Switzerland) · CHUniversity of St.Gallen · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paclitaxel/platinum chemotherapy, the backbone of standard first-line treatment of advanced non-small cell lung cancer (NSCLC), exhibits high interpatient variability in treatment response and high toxicity burden. Baseline blood biomarker concentrations and tumor size (sum of diameters) at week 8 relative to baseline (RS8) are widely investigated prognostic factors. However, joint analysis of data on demographic/clinical characteristics, blood biomarker levels, and chemotherapy exposure-driven early tumor response for improved prediction of overall survival (OS) is clinically not established. We developed a Weibull time-to-event model to predict OS, leveraging data from 365 patients receiving paclitaxel/platinum combination chemotherapy once every three weeks for ≤six cycles. A developed tumor growth inhibition model, combining linear tumor growth and first-order paclitaxel area under the concentration-time curve-induced tumor decay, was used to derive individual RS8. The median model-derived RS8 in all patients was a 20.0% tumor size reduction (range from -78% to +15%). Whereas baseline carcinoembryonic antigen, cytokeratin fragments, and thyroid stimulating hormone levels were not significantly associated with OS in a subset of 221 patients, and lactate dehydrogenase, interleukin-6 and neutrophil-to-lymphocyte ratio levels were significant only in univariate analyses (p value < 0.05); C-reactive protein (CRP) in combination with RS8 most significantly affected OS (p value < 0.01). Compared to the median population OS of 11.3 months, OS was 128% longer at the 5th percentile levels of both covariates and 60% shorter at their 95th percentiles levels. The combined paclitaxel exposure-driven RS8 and baseline blood CRP concentrations enables early individual prognostic predictions for different paclitaxel dosing regimens, forming the basis for treatment decision and optimizing paclitaxel/platinum-based advanced NSCLC chemotherapy.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsHumansPaclitaxelPlatinumPrognosisPaclitaxelPlatinum

Identifiers

PMID36782356
PMCPMC10681433
OpenAlexW4320710132

What OpenQuestion holds

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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.