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lapatinib + pegylated liposomal doxorubicin (Arbeitsgemeinschaft medikamentoese Tumortherapie)
- Development stage
- Unknown
- Lead developer
- GSK
- Modality
- Nanoparticles → Drug Delivery Systems, Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination therapy consists of lapatinib, a small-molecule dual tyrosine kinase inhibitor, and Caelyx (pegylated liposomal doxorubicin), a cytotoxic anthracycline. Lapatinib targets the intracellular kinase domains of both the epidermal growth factor receptor (EGFR/ErbB1) and the human epidermal growth factor receptor 2 (HER2/ErbB2), effectively blocking downstream signaling pathways involved in cell proliferation and survival. Caelyx utilizes a pegylated liposomal delivery system to prolong the circulation time of doxorubicin and enhance its accumulation in tumor tissues via the enhanced permeability and retention (EPR) effect. Once released, doxorubicin inhibits topoisomerase II and intercalates into DNA, leading to cell death. This regimen was specifically investigated by the Arbeitsgemeinschaft medikamentoese Tumortherapie (AGMT) in a Phase II clinical trial (NCT00954304) for patients with HER2-positive metastatic breast cancer who had failed prior trastuzumab-based therapy, aiming to provide an effective treatment with a manageable cardiotoxicity profile.
- Brand names
- TykerbCaelyxTyverbDoxil
- Other names
- lapatinib + doxorubicin hydrochloride liposomelapatinib + PLD
02
Targets
ERBB2 (Erb-b2 receptor tyrosine kinase 2)TOP2A (DNA topoisomerase II)EGFR (Epidermal growth factor receptor)DNA
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