Chemo Drugs 5 Flashcards
Imatinib mesylate
Class:
Macromolecular target:
MOA:
Pharmacokinetics and metabolism:
Side effects:
Class: tyrosine kinase inhibitor
Macromolecular target: Bcr-Abl fusion protein; c-kit
MOA:
- inhibits critical signaling pathway in the cancer cells that are constitutively active
- small molecule tyrosine receptor inhibitor
Pharmacokinetics and metabolism:metabolized in the liver by CYP3A4 system and excreted into the feces by the hepatobiliary
Side effects: superficial edema, nausea, muscle cramps, abdominal pain, musculoskeletal pain, rash, diarrhea, anemia, neutropenia, thrombocytopenia. Rarely congestive heart failure (not mention in lect)
Imatinib special features
given orally
- monitor thyroid function in hypothyroid patients taking thyroid replacement therapy. Imatinib may increase the clearance of thyroid hormone and dose may need to be increased
- Metabolized by CYP3A4-avoid coadministration with inducers and inhibitors
What is imatinib used for? others drugs in this category:
chronic myelogenous leukemia, gastrointestinal stromal tumor
Others: dasatinib and nilotinib
Cetuximab
Class:
Macromolecular target:
MOA:
Side effects:
Class: EGFR inhibitor
Macromolecular target: EGFR
MOA: Overexpression of EGFR receptors leads to increased signaling and affects cell growth and division and metastases to invasion
-also can sensitize the cell to effect of chemotherapy and can be used as a radiation therapy sensit
Side effects: hypersensitivity reactions, rash, diarrhea, hypomagnesemia
What are the special features and dose modifications of cetuximab?
Drug is a chimeric monoclonal antibody administered intravenously weekly or every other week as a single agent but usually in combination with chemo
What are the uses of cetuximab?
- lung cancer and head and neck cancer (patients not selected on basis of egfr expression)
- colorectal cancer: perform kras and nras are mutational analysis
- if wildtype =patient may respond
- if either is mutated- patient will not respond and it is not indicated
Erlotinib
Class:
Macromolecular target:
MOA:
Pharmacokinetics and metabolism:
Side effects:
Class: small molecule inhibitor of the tyrosine kinase domain associated with EGFR
Macromolecular target: Tyrosine kinase domain associated with EGFR
MOA: Inhibition of critical cell signaling pathways
Pharmacokinetics and metabolism: Metabolized by CYP3A4. avoid inducers and inhibitors
Side effects: Rash, Nausea, anorexia, fatigue
special features of erlotinib
- given orally
- metabolized by Cyp3A4
- Patients with Non-small cell lung cancer (ADENOCARCINOMA_BRONCHOALVEOLAR-woman, asian, never smoker) with activating mutation-should have erlotinib and is superior to chemo
- can make cancer cell more sensitive to TKI
bevacizumab
Class:
Macromolecular target:
MOA:
Side effects:
Class: VEGF inhibitor
Macromolecular target: VEGF ligand
MOA: monoclonal antibody binds to VEGF ligand and presumably decreases the growth of primary cancers and metastatic cancers due to impaired vasculature formation in the tumor
Side effects: infusion reactions, proteinuria, hypertension, arterial clots, bleeding, perforation of the colon, reversible posterior leukoencephalopathy syndrome rare
Special features of bevacizumab?
administered IV with chemotherapy. drug is not active as single agent
What are sorafenib, pazopanib, sunitinib?
multiple VEGF receptor tyrosine kinase inhibitors
- metabolized by CYP3A4
- oral administration
- similar toxicities as bevacizumab plus: hand food syndrome along with rashes, congestive heart failure (uncommon)
USES:
All Useful in renal cell cancer
Sunitinib-pancreatic neuroendocrine cancer, GI stromal tumor
Sorafenib-unresectable hepatocellular cancer
Trastuzumab
Class:
Macromolecular target:
MOA:
Side effects:
Target: extracellular domain of EGFR receptor, HER-2/neu
Intravenous administration with chemo
Fever, nausea, vomiting, diarrhea, cough, headache, SOB, back pain, rash and muscle pain, allergic reactions and infusion reactions
Heart failure: 1-4% of patients have clinical heart failure
- 34% have decline in cardiac function
- greatest risk in patients receiving concurrent anthracycline
- not dose dependent
- reversible(seems to be more forgiving that dox)
- potential for late problems unknown
- serial monitoring for cardiac ejection fraction
Crizotinib
Patients with ALK-anaplastic lymphoma kinase rearrangements had adenocarcinoma tend to be young and had little or no smoke exposure
- treated with crizotinib - 60Z% response rate and 33% stable disease
- perform mutational analysis on lung cancer patients for ALK rearrangements
Vemurafenib
40-60% of patients with melanoma have an activating mutation in the gene coding for BRAF. The mutation causes constitutively active phosphorylation of downstream signaling
- vemurafenib inhibits mutated braf
- oral drug
- mutational analysis in melanoma cnares (V600e mutation in braf
L-asparagine
Depletes asparagine pool rapidly
- leukemia cells lack asparagine synthetase and cannot synthesize asparagine
- cellular effects due to decrease in protein syntheiss
- allergic reactions liver enzyme elevations, clotting (due to decrease in antithrombin 3 levels), pancreatitis and elevated glucose
-useful in treatment of acute lymphoblastic leukemia
