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Cisplatin, Docetaxel, and Nintedanib

Development stage
Unknown
Lead developer
Michigan State University
Modality
Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration
Intravenous, Oral
01

Overview

The combination of cisplatin, docetaxel, and nintedanib represents a multi-drug regimen used primarily in the treatment of non-small cell lung cancer (NSCLC). ## Mechanism and Clinical Use This combination therapy brings together three distinct agents with complementary mechanisms of action: 1. **Nintedanib** is a tyrosine kinase inhibitor that targets multiple receptors including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). It blocks the formation of new blood vessels that tumors need to grow and spread[4][6]. 2. **Docetaxel** is a chemotherapy agent commonly used in NSCLC treatment, particularly as a second-line option. When combined with nintedanib, it has shown clinical benefit in adenocarcinoma patients[4]. 3. **Cisplatin** is a platinum-based chemotherapy agent that works by damaging DNA and preventing cancer cell replication. ## Clinical Evidence The LUME-Meso trial investigated nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma[7]. While this specific trial used pemetrexed rather than docetaxel, it demonstrates the concept of combining nintedanib with platinum-based chemotherapy. Several clinical trials have shown that nintedanib plays a substantial role in treating NSCLC patients, particularly when combined with other agents[4]. Meta-analyses have indicated that nintedanib combined with docetaxel provides clinical benefit as a second-line treatment for adenocarcinoma patients[4]. ## Side Effects The combination therapy may cause various side effects including: - Liver changes (ranging from mild to serious) - Gastrointestinal issues (diarrhea, nausea, vomiting, abdominal pain) - Numbness or tingling in fingers or toes - Potential cardiovascular events - Bleeding problems[7] These side effects require careful monitoring, particularly liver function tests during treatment. ## Development Status This combination has been studied primarily in advanced non-small cell lung cancer of adenocarcinoma histology, with particular focus on patients who have already received first-line therapy[2][4].

02

Targets

VEGFR1/2/3 (Vascular endothelial growth factor receptor 1 (VEGFR1) / Vascular endothelial growth factor receptor 2 (VEGFR2) / Vascular endothelial growth factor receptor 3 (VEGFR3))PDGFRA (Platelet-derived growth factor receptor alpha)DNAFGFR2 (Keratinocyte growth factor receptor)FLT3 (Fms related receptor tyrosine kinase 3)

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