Review of Pharmacology - 9E (2015)

Review of Pharmacology
Chemotherapy C: Antineoplastic Drugs
642
Imatinib is the drug of choice for
CML and gastro-intestinal stromal
tumor (GIST).
N
TK inhibitors for NSCLC
After – Afatinib
E – Erlotinib
C – Crizotinib
– Ceritinib
G – Geftinib
N
TK inhibitors for RCC
P – Pazopanib
A – Axitinib
S – Sorafenib
S – Sunitinib
N
TK inhibitors for malignant
melanoma
D – Dabrafenib
V – Vemurafenib
T – Trametinib
N
TK inhibitors for GIST
S – Sunitinib
I – Imatinib
R – Regorafenib
Note: All natural anticancer products can cause bone marrow suppression except bleomycin and
vincristine.
Tyrosine Kinase Inhibitors
• Imitinab is an oral drug used for chronic phase of CML. It acts by inhibiting
tyrosine kinase activated due to abl-bcr fusion (t 9, 22; Philadelphia chromosome).
It is a competitive inhibitor of ATP-binding of the abl kinase in the inactive
conformation. Dasatinib and Nilotinib are similar drugs used in case of imatinib
resistance. Imatinib is the drug of choice for CML and gastro-intestinal stromal
tumor (GIST).
• Geftinib and Erlotinib are inhibitors of tyrosine kinase associated with epidermal
growth factor receptor (EGFR). These are indicated for non-small cell lung cancer.
Erlotinib is especially effective in cases affecting women, nonsmokers, and persons of
Asian ethnicity as well as cases involving adenocarcinoma and bronchioalveolar carcinoma
histology. Erlotinib is also indicated for pancreatic carcinoma with gemcitabine.
Food increases the absorption of Erlotinib to 100%. It is metabolized by CYP3A4
enzyme system. Acneiform skin rash, diarrhea, anorexia and fatigue are the most
common adverse effects of this drug. Molecular studies have shown that patients
with EGFR mutations respond to Erlotinib at significantly high rates, but patients
with Kras mutations do not respond and should not be offered this drug.
• Sorafenib and Sunitinib are small molecules that inhibit multiple tyrosine kinases.
Both can be used for renal cell cancer. In addition sorafenib is indicated for hepatocellular
cancer and sunitinib for GIST. These can cause hypertension as an adverse effect.
• Lapatinib is indicated for breast carcinoma. It inhibits tyrosine kinase associated
with EGFR and her-2/neu receptors.
• Pazopanib is a multi targeted tyrosine kinase inhibitor against VEGF receptors,
PDGF receptor and c-kit. It is approved for treatment of advanced renal cell
carcinoma.
• All tyrosine kinase inhibitors are metabolized by CYP 3A4 enzymes. Thus, these
have the potential of drug interactions.
• All tyrosine kinase inhibitors can be administered orally.
Drug Inhibit TK activated by Indication
Afatinib EGFR, HER-2, HER-4 Non-small cell lung carcinoma (NSCLC)
Axitinib VEGFR-1,2,3 Advanced renal cell carcinoma
Bosutinib abl-bcr, src CML
Ceritinib ALK NSCLC
Crizotinib c-MET, ALK Non-small cell lung carcinoma
Cabozantinib c-MET, VEGFR-2 Medullary carcinoma thyroid
Dabrafenib BRAF Metastatic melanoma
Dasatinib abl-bcr CML
Erlotinib EGFR Non-small cell lung carcinoma
Pancreatic carcinoma
Geftinib EGFR Non-small cell lung carcinoma
Ibrutinib Btk CLL
Imatinib abl-bcr, c-KIT, PDGF CML
GIST
Lapatinib her-2/neu, erb-B2 Breast carcinoma
Lenvatinib VEGF I 131 refractory differentiated thyroid cancer
Nilotinib abl-bcr CML
Pazopanib VEGFR-1,2,3 PDGFR α, β c-KIT Advanced renal cell carcinoma
Contd...
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