Skin Cancer Chemotherapeutic Agents Flashcards
What is Pembrolizumad (Keytruda) Pem bro lee zoo mab
A monoclonal antibody (IgG4) that I a PD-1 Check point inhibitor (binds to the receptor on the T and B cell’s surface preventing the binding of the Programed death - ligand 1 “PD-1” ) that prevents T-cell deactivation so they can continue to proliferate.
What skin cancer is Pembrolizumad (Keytruda) FDA approved to treat?
Melanoma. Also has been used in SCC and Merkel cell carcinoma.
How is Pembrolizumad (Keytruda) given?
IV
Lichenoid and Spongiotic eruptions associated with Pembrolizumad (Keytruda) in 17% of patients are due to what.
Robust immune response.
What is Vemurafenib (Zelboraf)?
BRAF inhibitor that targets the MAPK pathway causing programmed cell death in melanoma.
What mutation which 60% of melanomas have for Vemurafenib to be effective?
V600E BRAF mutation.
What type of skin lesions may Vemurafenib cause?
SCCs, KAs and benign verrucous keratoses
What skin cancer drug targets toll-like receptors 7 &8
Imiquimod/Aldara
What does binding to toll like receptors do?
Stimulates production of interferon gamma which activates T1 helper cells causing pro inflammatory cytokines to be released.
What is the mechanism of action of Cemiplimab.
monoclonal antibody that binds to a program death-1
receptor (PD-1 ) on T-cells preventing the PD-1 ligand to attach. The PD-1 ligand suppresses the T-Cell. Cemiiplimab cause the T-cells to proliferate.
What is the generic name of Libtayo
Cemiplimab Seme plab nab
How is Cemiplimab Libtayo delivered
IV
How do you pronounce Pembrolizumab
Pem bro lee zoo mab
What does Atezolizumab do?
In melanoma the IgG1 antibody binds to the PD-L1 ligand which prevents it from binding to the receptor on the activated T and B cells thereby stopping inhibition of proliferation of these cells.
How do you pronounce Atezolizumab?
Ah teza liz a mab
How does Talimogene laherparepvec (T-VEC) work.
It’s an oncolytic herpes virus injected into a inoperable tumor.
How does Ipilimumab work?
its a monoclonal antibody which binds to CTL4 causing up regulation of the immune system in melanoma and other cancers.
how you pronounce Ipilimumab
ip e lee myoo mab
What is the half life of etretinate?
120 days
How long does one have to be on birth control after etretinate?
3 years
What is the dosage interval for Calcipotriol + 5FU for AKs
Bid application for four days.
Imiquimod has what mechanism of action.
Binds to TLR7 (Toll like receptor) on immune cells to activate them. TLR7 binds to single stranded RNA in defence against viruses. Increases immunity.
What is the dosage for Imiquimod for TX of AKs.
3 x week for 12-16 wks
What is the dosage for Imiquimod for BCC
5x week for 6 weeks
What is the dosage for Imiquimod for Melanoma in situ
5x week for 12 weeks
What is the brand name for Ingenol Mebutate
Picato
what is the mechanism of action of Ingenol Mebutate?
Activates protein kinase delta C causing direct cell death.
What is the treatment and dose for Ingenol Mebutate? on the face.
.015 gel for three days.
What is the treatment and dose for Ingenol Mebutate? on the arms.
.05 gel for two days
what is the dosage for 5FU in treating AKs
5% cream BID for 2 weeks.
what is the mechanism of action of 5FU
inhibits Thymine synthesis
What are the two PDT drugs.
5aminolevulinic acid (5ALA) Methyl aminolevulinate MAL
What wavelength does 5 aminolevulinic acid work best at?
405 blue light The soret band 405-420
What wavelength does Methyl aminolevulinic acid acid work at?
635 red light
What is the mechanism of action of PDT
drugs are selectively taken up by cancer cells and converts into protoporphyrins IX. Porphyrins when activated by light become toxic.
Which penetrates deeper red or blue light tx?
Red light more than 2mm.
5FU and calcipotriol (vit D) TX has what percentage of new SCCs in 3 years.
7%
Why might 5FU and Calcipotriol have a prolonged effect.
Increase in epidermal resident memory T cells (Trm)
For superficial BCC which has the highest cure rate at 3 years. PDT, imiquimod, 5FU
- Imiquimod 79%
- 5FU 68%
- PDT 58%
How does Vismodegib and Sonidegib work for BCC?
In the hedgehog pathway they inhibit smoothened transmembrane receptor.
Which of Vismodegib and Sonidegib is not FDA approved for metastatic BCC.
Sonidegib
Which of Vismodegib and Sonidegib has a higher complete response rate?
Vismodegib 28%
Sonidegib 9%
What are the brand names of Vismodegib and Sonidegib?
Vismodegib ERIVedge
Sonidegib Odomzo
What are the four most common side effects of Vismodegib and Sonidegib?
- Muscle spasms 67%
- Alopecia 58%
- Dysgeusia 54%
- weight loss
Which of Vismodegib and Sonidegib is more likely to cause muscle spasms with elevated creatinine kinase?
Sonidegib (Odomzo)
Which of Vismodegib and Sonidegib are teratogenic?
Both, both extremely.
What is the contraception period after taking Vismodegib or Sonidegib .
20 months women
8 months men
How is sonidegib metabolized?
cytochrome P450 (drug interactions)
Median tumor resistance develops in Vismodegib and Sonidegib for localized disease and Met disease in how many months
22 localized
10 mets
for Sonidegib what labs should be monitored before and during treatment?
CK levels creatine kinase
two treatments for dysgeusia associated with hedgehog pathway blockers.
tetrahydrocannabinol
zinc
what may reduce side effects and increase durability with Vismodegib and Sonidegib
intermittent dosage.
nibs do what
BRAF inhibitors
Name two types of immunotherapy that are cytokines that increase T cells and their response against melanoma.
Interferon and Interleukin 2
In targeted therapy for melanoma what is targeted?
MAPK pathway (which regulates cell proliferation)
What are the 5 steps in the MAPK pathway.
NRA - BRAF -MEK -ERK -gene transcription
what drugs work on the MAPK pathway in treating melanoma.
nibs
What is the most common gene mutated in the MAPK pathway
BRAF V600E
What two components of the MAPK pathway do nibs block.
BRAF and MEK
What are the two nibs that block BRAF
Vemura fe and Dabra fe and encora fe
What are the two nibs that block MEK
Tra met and Cobi met and Bimi met
What is one side effect in blocking BRAF
increase in SCC and BCC
What are two side effects in blocking MEK
photosensitivity and acne
Why are BRAF and MEK inhibitors given together?
less side effects and longer duration
How fast is onset with BRAF and MEK inhibitors?
6 weeks
What is the normal duration of response to BRAF and MEK inhibitors?
1 to 1 1/2 years
What % of melanomas are BRAF + meaning have the BRAF mutation?
50%
What are the check point inhibitors for melanoma
umabs
Are checkpoint inhibitors targeted therapy or immunotherapy?
Immunotherapy
What does ipilimumab block
CTLA-4 (which is a negative regulator of T cell immune function)
What is tirbanibulin
5 day topical treatment for AKs
What drug is a microtubule inhibitor used in the treatment of AKs
tribanibulin
What is the brand name of tirbanibulin
Klisyri
What did cemiplimab just get approved for.
Treatment of BCC. Was already approved for advanced cutaneous SCC
What drug targets the CTLA-4 receptor on T-cells to reinvigoration of the T-cells to attack melanoma
Ipilimumab
What does vismodegib inhibit
smoothened in the sonic hedgehog pathway
5FU is an antagonist to what?
pyrimidine synthesis
what is the mechanism of action for Ipilimumab
Targets the CTLA-4 receptor on T cells
What does Mycophenolate mofetil (MMF) do?
it is an immunosuppressant for renal transplants it blocks purine synthesis. It is used off label as a steroid sparing drug for autoimmune diseases.
what is vorinostat
it is a histone inhibitor used in MF
What is the most common mutated gene in the MAPK pathway?
BRAF V600E
what is the two year survival on ipilimumab and Nivolumab
60%
which of the two has a higher cure rate for BCC and which has more systemic toxicities? Imiquimod and 5FU
Imiquimod higher cure rate and higher systemic toxicity.
Do NSAIDs taken 8+ times a week increase risk for SCC and AKs
no, it decreases risk
