Management of atrial fibrillation in patients taking targeted cancer therapies

Asnani, Aarti; Manning, Anastasia; Mansour, Moussa; Ruskin, Jeremy; Hochberg, Ephraim P.; Ptaszek, Leon M.

doi:10.1186/s40959-017-0021-y

Table 1 Pharmacokinetics of commonly used targeted cancer therapies

From: Management of atrial fibrillation in patients taking targeted cancer therapies

Tyrosine Kinase Inhibitors	Molecular Target(s)	FDA-Approved Indications	Clinically Significant Drug Metabolism/Elimination	Clinically Significant Adverse Effects
Afatinib	ErbB family (EGFR, HER-2,-4)	NSCLC	P-gp substrate
Axitinib	VEGFR-1,-2,-3	RCC	CYP3A4 substrate
Bosutinib	BCR-ABL, SRC family (SRC, LYN, HCK), c-KIT, PDGFR	CML	CYP3A4 substrate; P-gp inhibitor	QT prolongation
Cabozantinib	HGFR, RET, VEGFR-1, −2, −3, KIT, FLT3, TIE-2, TRKB, AXL	Medullary thyroid cancer	CYP3A4 substrate
Ceritinib	ALK, IGF-1R, InsR, ROS1	NSCLC	CYP3A4 substrate & strong inhibitor; P-gp substrate	QT prolongation Bradycardia
Crizotinib	ALK, HGFR, RON	NSCLC	CYP3A4 substrate & moderate inhibitor; CYP2B6 moderate inhibitor; P-gp substrate and inhibitor	QT prolongation Bradycardia
Dasatinib	SRC family (SRC, LCK, YES, FYN), BCR-ABL, c-KIT, EPH-A2, PDGFR-β	ALL, CML	CYP3A4 substrate & weak inhibitor	QT prolongation
Erlotinib	EGFR	NSCLC, Pancreatic cancer	CYP3A4 substrate
Gefitinib	EGFR	NSCLC	CYP3A4 substrate; CYP2D6 substrate
Ibrutinib	BTK	CLL, MCL, WM	CYP3A4 substrate; P-gp inhibitor
Imatinib	BCR-ABL, c-KIT, PDGFR, SCF	ALL, CEL, CML, GIST, ASM, DFSP, MDS/MPD	CYP3A4 substrate & moderate inhibitor; P-gp substrate
Lapatinib	EGFR, HER2	Breast cancer	CYP3A4 substrate; CYP2C8 moderate inhibitor; P-gp substrate & inhibitor	QT prolongation
Lenvatinib	VEGFR-1,-2,-3, FGFR-1,-2,-3,-4, PDGF-α, KIT, RET	Thyroid cancer		QT prolongation
Nilotinib	BCR-ABL, PDGFR, c-KIT	CML	CYP3A4 substrate & moderate inhibitor; CYP2D6 moderate inhibitor; CYP2C8 moderate inhibitor; P-gp inhibitor	QT prolongation
Osimertinib	EGFR	NSCLC	CYP3A4 substrate; BRCP inhibitor	QT prolongation
Pazopanib	VEGFR-1,-2,-3, PDGFR-α,-β, FGFR-1,-3, c-KIT, IL-2 inducible TcK, Lck, c-Fms	RCC, STS	CYP3A4 substrate; P-gp substrate	QT prolongation
Ponatinib	BCR-ABL, VEGFR, FGFR, PDGFR, EPH, SRC, KIT, RET, TIE2, FLT3	ALL, CML	CYP3A4 substrate
Regorafenib	VEGFR-1,-2,-3, KIT, PDGFR-α,-β, RET, FGFR-1,-2, TIES2, DDR2, TrkA, EPH-A2, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, ABL	Colorectal cancer, GIST	CYP3A4 substrate	Bradycardia
Ruxolitinib	JAK-1,-2	Myelofibrosis, Polycythemia vera	CYP3A4 substrate	Bradycardia
Sorafenib	RAF, VEGFR-1,-2,-3, PDGFR-β, c-KIT, FLT-3, RET, RET/PTC	RCC, HCC, Thyroid carcinoma	CYP2C9 moderate inhibitor; CYP2B6 moderate inhibitor	QT prolongation
Sunitinib	PDGFR-α,-β, VEGFR-1,-2,-3, FLT3, CSF-1R, RET	RCC, GIST, PNET	CYP3A4 substrate; P-gp inhibitor	QT prolongation
Vandetanib	EGFR, VEGFR, RET, BRK, TIES2, EPH, SRC	Medullary thyroid cancer	P-gp inhibitor	QT prolongation

ALK anaplastic lymphoma kinase, BCR-ABL fusion gene, BRAF B-Raf Proto-Oncogene, Serine/Threonine Kinase, BRK protein tyrosine kinase 6, BTK Bruton’s Tyrosine Kinase, c-Fms transmembrane glycoprotein receptor tyrosine kinase, c-KIT cytokine receptor, CSF-1R colony-stimulating factor type 1, DDR2 discoidin domain receptor 2, EGFR epidermal growth factor receptor, EPH Ephrin Receptor, ErbB family of tyrosine kinase inhibitors, FGFR fibroblast growth factor receptor, FLT FMS-like Tyrosine Kinase, HCK Hemopoietic cell kinase, HER human epidermal growth factor receptor, HGFR hepatocyte growth factor receptor, IGF-1R insulin-like growth factor 1 receptor. IL-2 inducable, TCK interleukin-2 receptor inducible T-cell Kinase, InsR insulin receptor, JAK Janus Associated Kinases, Lck Leukocyte-specific Protein Tyrosine Kinase, PDGFR platelet-derived growth factor receptor, PTK protein tyrosine kinase 2 beta, RET “Rearranged During Transfection”, RON Recepteur d’Origine Nantais, SCF stem cell factor, TIE Tyrosine Kinase with Immunoglobulin-like and EGF-like Domains, VEGFR vascular endothelial growth receptor, ALL acute lymphoblastic leukemia, ASM aggressive systemic mastocytosis, CEL chronic eosinophilic leukemia, CML chronic myeloid leukemia, DFSP Dermatofibrosarcoma Protuberans, GIST gastrointestinal stromal tumor, HCC hepatocellular carcinoma, MCL mantle cell lymphoma, MDS/MPD myelodysplastic syndrome/myeloproliferative disease, NSCLC non-small cell lung cancer, PNET pancreatic neuroendocrine tumor, RCC renal cell carcinoma, STS soft tissue sarcoma, WM Waldenstrom’s Macroglobulinemia, BRCP breast cancer resistance protein, P-gp P-glycoprotein

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