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

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 r...

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Published in:CPT: pharmacometrics and systems pharmacology 2023-11, Vol.12 (11), p.1714-1725
Main Authors: Ojara, Francis Williams, Henrich, Andrea, Frances, Nicolas, Nassar, Yomna M., Huisinga, Wilhelm, Hartung, Niklas, Geiger, Kimberly, Holdenrieder, Stefan, Joerger, Markus, Kloft, Charlotte
Format: Article
Language:English
Subjects:
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers
Cancer therapies
Carcinoma, Non-Small-Cell Lung
Chemotherapy
Drug dosages
Growth models
Humans
Lung cancer
Lung Neoplasms - pathology
Medical prognosis
Oncology
Paclitaxel
Patients
Pharmacokinetics
Platinum - therapeutic use
Prognosis
Tumors
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Summary: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 
ISSN:2163-8306
2163-8306
DOI:10.1002/psp4.12937