Improving the Response to Lenvatinib in Partial Responders Using a Constrained-Disorder-Principle-based Second-generation Artificial Intelligence-therapeutic Regimen: a Proof-of-concept Open-labeled Clinical Trial
Overview
Authors
Affiliations
Introduction: The main obstacle in treating cancer patients is drug resistance. Lenvatinib treatment poses challenges due to loss of response and the common dose-limiting adverse events (AEs). The Constrained-disorder-principle (CDP)-based second-generation artificial intelligence (AI) systems introduce variability into treatment regimens and offer a potential strategy for enhancing treatment efficacy. This proof-of-concept clinical trial aimed to assess the impact of a personalized algorithm-controlled therapeutic regimen on lenvatinib effectiveness and tolerability.
Methods: A 14-week open-label, non-randomized trial was conducted with five cancer patients receiving lenvatinib-an AI-assisted application tailored to a personalized therapeutic regimen for each patient, which the treating physician approved. The study assessed changes in tumor response through FDG-PET-CT and tumor markers and quality of life via the EORTC QLQ-THY34 questionnaire, AEs, and laboratory evaluations. The app monitored treatment adherence.
Results: At 14 weeks of follow-up, the disease control rate (including the following outcomes: complete response, partial response, stable disease) was 80%. The FDG-PET-CT scan-based RECIST v1.1 and PERCIST criteria showed partial response in 40% of patients and stable disease in an additional 40% of patients. One patient experienced a progressing disease. Of the participants with thyroid cancer, 75% showed a reduction in thyroglobulin levels, and 60% of all the participants showed a decrease in neutrophil-to-lymphocyte ratio during treatment. Improvement in the median social support score among patients utilizing the system supports an ancillary benefit of the intervention. No grade 4 AEs or functional deteriorations were recorded.
Summary: The results of this proof-of-concept open-labeled clinical trial suggest that the CDP-based second-generation AI system-generated personalized therapeutic recommendations may improve the response to lenvatinib with manageable AEs. Prospective controlled studies are needed to determine the efficacy of this approach.
Inter-organ correlations in inflammation regulation: a novel biological paradigm in a murine model.
Shabat Y, Rotnemer-Golinkin D, Zolotarov L, Ilan Y J Med Life. 2025; 18(1):67-72.
PMID: 40071160 PMC: 11891616. DOI: 10.25122/jml-2024-0246.
Ilan Y J Pers Med. 2025; 15(1).
PMID: 39852203 PMC: 11767140. DOI: 10.3390/jpm15010010.
Ilan Y Bioengineering (Basel). 2024; 11(11).
PMID: 39593770 PMC: 11592301. DOI: 10.3390/bioengineering11111111.
Sigawi T, Israeli A, Ilan Y Immunotargets Ther. 2024; 13:525-539.
PMID: 39431244 PMC: 11488351. DOI: 10.2147/ITT.S477841.