Drug intelligence / Profile preview

doxorubicin + cyclophosphamide + sunitinib

Development stage
Phase 2
Lead developer
Pfizer
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination treatment regimen investigated in clinical trials for breast cancer, particularly locally advanced breast cancer (LABC) and inflammatory breast cancer (IBC). It combines traditional chemotherapy agents, **doxorubicin** (an anthracycline topoisomerase II inhibitor) and **cyclophosphamide** (an alkylating agent), with a targeted therapy, **sunitinib** (a multi-targeted receptor tyrosine kinase inhibitor). Clinical trials have evaluated different schedules, including sunitinib administered with paclitaxel followed by doxorubicin and cyclophosphamide, or sunitinib given before cycles of doxorubicin and cyclophosphamide. Phase II trials have shown varying efficacy results. One trial did not meet its primary endpoint of improving pathologic complete response (pCR) rate, achieving a pCR rate of 27%. Another study found similar pCR rates with the addition of sunitinib compared to chemotherapy alone (5.0% vs 4.3%). Common toxicities include cytopenias and fatigue. The addition of sunitinib has been associated with significantly more dose delays and grade 3/4 non-hematologic toxicities such as stomatitis, non-neutropenic fever, and lethargy. The potential role of this combination, particularly for ER-positive LABC, requires further investigation.

Other names
sunitinib + ACAC + sunitinib
02

Targets

CSF1R (Macrophage colony-stimulating factor receptor)DNAFLT3 (Fms related receptor tyrosine kinase 3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)TOP2A (DNA topoisomerase II)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)

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