B.37. Cancer chemotherapy VI (large molecule signal transduction inhibitors) Flashcards
list the signal transduction inhibitors (large molecules)
Trastuzumab Panitumumab Rituximab Bevacizumab Pembrolizumab IFN- 𝝰 Aldesleukin
what is Trastuzumab?
-anti-HER2/neu receptor
(epidermal growth factor receptor)
-Humanized monoclonal Ab
which Ab are humanized monoclonal Ab?
trastuzumab
Bevacizumab
Pembrolizumab
which Ab is a chimeric monoclonal Ab?
Rituximab
which Ab is a human monoclonal Ab?
Panitumumab
what is Trastuzumab-emtansine?
Antibody-drug conjugate:
trastuzumab covalently linked to the cytotoxic agent emtansine (DM1)
what does emtansine do?
binds tubulin and cause mitotic arrest–> cell death
indications for Trastuzumab (+emtansine)
breast cancer (HER2 +)
side effects of Trastuzumab
injection-site reaction
nausea, vomiting
cardiotoxicity (reduced EF, CHF)
what is Panitumumab and Cetuximab?
anti-EGFR
human monoclonal Ab
what is the indication of Panitumumab?
colon cancer (metastatic disease, K-RAS wild type)
what tumors are resistant to Panitumumab?
mutated K-RAS tumors
side effects of Panitumumab
dermatologic symptoms
nausea, vomiting
diarrhea
which agents do we give in combination with Panitumumab?
Irinotecan
fluorouracil
leucovorin
(FOLFIRI protocol)
what is Rituximab?
Anti-CD20 (expressed on B-cells)
chimeric monoclonal Ab
what is the mechanism of Rituximab?
binding on B cells–> induces complement-mediated lysis–> direct cytotoxicity and induction of apoptosis–> B- cell count ↓
indications of Rituximab
Non-Hodgkin's B cell lymphoma CLL post-transplant lymphoma immune-mediated diseases (RA, AIHA,ITP, TTP) Wegner granulomatosis
side effects of Rituximab
- hypersensitivity reaction
* infusion reaction
* serum sickness - tumor lysis syndrome
- myelosuppression
- risk of latent infections (JC virus, HBV)
what is Bevacizumab?
anti-VEGF (anti-angiogenesis agent)
humanized monoclonal Ab
indications for Bevacizumab?
colon cancer
breast cancer
non-small lung carcinoma
renal cancer
Side effects of Bevacizumab
hypertension impaired wound healing injection site reaction arterial thromboembolism Gi perforation (rare)
What is Pembrolizumab?
- immunomodulator (check-point protein modulator)
- Antibody binds PD-1 Receptor of lymphocytes (programmed cell death protein 1)–> blocks T cell activation
- Humanized monoclonal Ab (IgG₄ isotype)
when do we give Pembrolizumab?
melanoma
non-small cell lung carcinoma
side effects of Pembrolizumab?
injection site reaction
pneumonitis
inflammation of endocrine glands
what is IFN-𝝰?
cytokine with antineoplastic, antiviral, immunosuppressive properties
what does IFN-𝝰 do?
binds to a specific receptor on the cell membrane
induces gene transcription
inhibits cellular growth
very cytotoxic–> cell death
when do we use IFN-𝝰?
CLL Hairy-cell leukemia T-cell lymphomas AIDS-related Kaposi sarcoma HPV, HBV, HCV
Side effects of IFN-𝝰
Flu-like symptoms
myelosuppression
neurotoxicity
Fever, alopecia
*damage to all organs
what is Aldesleukin?
IL-2 recombinant protein
stimulates growth and differentiation of T, B, NK Cells
when do we give Aldesleukin?
Renal cancer
Melanoma
side effects of Aldesleikin
Diarrhea
hypotension
capillary leak syndrome (CLS)
