Table 2.
Main characteristics of the major angiogenesis inhibitors and possible pharmacokinetics interactions $ [46].
| Drug (alias) | Targets (Type) | Metabolic Route | Possible N/DS Interactions | Pharmacogenomics-Based Warnings |
|---|---|---|---|---|
| Bevacizumab | VEGF (mAb) | Serum esterase | ND | ND |
| Brivanib | VEGFR, FGF (TKIs) |
ND | ND | |
| Cabozantinib | c-MET, RET, VEGFR1-3, c-KIT (TKIs) |
CYP3A4 CYP2C8 |
Food and N/SD alter PK | Acquired mutation on FLT-3 ITD, c-Kit D816V |
| Cediranib | VEGFR-2, PDGFR, c-KIT (TKIs) |
UGTA1A, FMO1, FMO3 |
Food and N/SD alter PK | ND |
| Everolimus | m-TOR | CYP2C19 CYP3A4 |
Grapefruit juice can increase the blood levels and effects of everolimus | Screening for SNPs CYP2C19*2, *3 and *17 |
| Lenvatinib | VEGFR1-3, FGFR-1, PDGFRα, RET, KIT (TKIs) | ND | acquired VEGFR-2 mutation | |
| Linfantib | VEGFR-2, PDGFRs (TKIs) | ND | ND | ND |
| Nintedanib | VEGFR-1-3, FGFR-1, PDGFR (TKIs) |
ND | ND | ND |
| Ramucirumab | Selective VEGFR-2 mAb | Serum esterase | ND | ND |
| Refametinib | MEK 1-2, MAPK inhibitor |
ND | ND | ND |
| Regorafenib | VEGFR1-3, c-KIT, TK Ig-like, EGF-like PDGF-2, FGF-1, RET, BRAF, MAPK (TKIs) | ND | ginger | ND |
| Sorafenib | VEGFR-2, PDGFR, c-KIT, BRAF (TKIs) |
CYP3A4, CYP3A5 | black cohosh, cascara sagrada, senna, St. John’s wort | ND |
| Sunitinib | CYP3A4 | St. John’s wort | Dose reductions for CYP3A4 Poor Metabolizers | |
| Trebananib | TIE-2 (Ang) AI |
ND | ND | |
| Vatalanib | VEGFR-1,-2,-3, PDGFRs, c-FMS (TKIs) | CYP3A4 | ND | ND |
$ Source: https://www.drugbank.ca/drugs/DB11958. Abbreviation: Cytochrome P450 family (CYP); Receptors for growth factors (VEGFR, FGFR, PDGFR); tyrosine kinases (TKs) and the downstream RAS/RAF/mitogen-activated protein extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK). Pharmacokinetic (PK); not described (ND).