1.16 - Treatment of Melanoma Flashcards
ABCDE of Melanoma
o Asymmetry o Border irregularity o Color variation o Diameter >6 mm o Evolution (lesion on skin has change over time)
Overall treatment modality
Immunotherapy because it is one of the cancers considered most resistant to traditional treatment modalities.
Interferon: Types of Intereferon Drugs.
1) Interferon-alfa 2b
(Intron A®)
2) Peginterferon-alfa 2a
(Pegasys ®)
3) Peginterferon-alfa 2b
(Sylatron ®)
Interferon Toxicity: One of the adverse effects is fatigue, what do you want to test when a patient presents with it?
Check thyroid function to make sure fatigue is not caused by something else.
Interferon Toxicity: 7 main toxicities
Flu like symptoms
Fatigue
Hepatotoxicity = assess liver function
Anorexia, weight loss, etc.
Neuropsychiatric symptoms = do not give to patients diagnosed with major depression
Ocular Toxicity = Retinal hemorrhages, optic neuropathy, etc. Caution in diabetic patients
Autoimmunity: Thyroid dysfunction and pancreatic (hyperglycemia)
Biggest Side Effect of Interleukin-2
Capillary leak syndrome
What is the MOA target of Ipilimumab?
Binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
o T-cell medicated antitumor immune response
What is the MOA target of Vemurafenib?
Kinase inhibitor of some forms of BRAF serine-threonine kinase, including mutated BRAF V600E (see commonly in melanoma)
Common toxicities of Ipilimumab
1) Enterocolitis
2) Hepatitis
3) Dermatitis
4) Neuropathies
5) Endocrinopathies
Note: Give Systemic corticosteroids for Side Effects
What is BRAF?
A critical regulator of cell growth and survival. Apparently overall mutation rate of this gene is really high in melanoma.
- Expression results in constitutive phosphorylation of MEK and MAPK
Chemotherapy agents that need to be taken on an empty stomach (2)
Dabrafenib(?) and Trametinib
Which drugs do you want to give if melanoma is BRAF V600E mutation positive?
Vemurafenib, Dabrafenib or Trametinib
Note: Dabrafenib is updated form of Vemurafenib.
What is important about the relationship between Dabrafenib and Trametinib?
- Dabrafenib (Vemurafenib) target BRAF while Trametinib target MEK pathway.
Dabrafenib and trametinib target 2 different tyrosine kinases in the RAS/RAF/MEK/ERK pathway (so beneficial to use in combination)
What are the PD-1 Drugs? (2)
Pembrolizumab and Nivolumab
MOA of Pembromilizumab and Nivolumab
Monoclonal antibody that acts as an immune checkpoint inhibitor by binding to the human programmed death-1 (PD-1) receptor on T-cells and blocking the PD-1 interaction with PD-1 ligands.
o Allowing activated tumor-specific T-cells to kill tumor cells and secrete cytokines to restore antitumor immune responses
Resulting in decreased tumor growth
