skin cancer drugs Flashcards
what are the conventional chemo drugs used for tx of basal cell carcinoma? (6)
cisplatin, cyclophosphamide
doxorubicin,fluorouracil
methtrexate, vinblasatine
conventional chemo drugs for squamous cell carcinoma?(1)
cisplatin
conventional chemo drugs for melanoma?(6)
think: D-drugs except doxo, microtubule inhibitors
carmustine
dacarbazine, dactinomycin, docetaxel
lomustine, vinblastine
conventional drugs for actinic keratosis?(1)
fluorouracil
targeted and other therapeutics for basal cell carcinoma?(2)
imiquimod and vismodegib
targeted therapies for squamous cell carcinoma?
NONE
targeted therapies for melanoma?(6)
aldesleukin interferon ipilimumab sorafenib trametinib vemurafenib
targeted therapy for actinic keratosis?(3)
diclofenac
imiquimod
trichloroacetic acid
conventional chemo most commonly used for which two cancers?
BCC and melanoma
t/f. most skin cancers are cured if found and treated early
true
two topical treatments for localized BCC?
fluorouracil and imiquimod
BCC advanced or metastatic disease is rare. What is the most common standard chemo for this disease? targeted drug?
standard: cisplatin
targeted: vismodegib
imiquimod MOA?
Immunostimulant
- TLR7 and/or TLR8 agonist–>Th1 immune response by activating sentinel cells in the vicinity of the tumor
- involvement of adenosine receptor blockade
- activation of NF-KappaB-upregulation of cytokines like TNFalpha and interleukins
imiquimod indications
BCC, also actinic keratosis and HPV
Imiquimod ADME:
topical agent; limited systematization
imiquimod ADE? pregancy category?
photosensivity; contact can compromise condom and diaphragm integrity
Category C
Imiquimod MOA independent of TLR7/8 activation?
hedgehog singaling repressor
what is hedgehog signaling?
pathway that regulated body patterning and organ development (mainly quiescent by adulthood except for a role in tissue repair)
MOA of vismodegib
oral SMO(smoothened = protein by which HH signals travel) inhibitor
ADME of vismodegib
lipohillic agent with extensive metabolism
the 3 black box warnings of vismodegib
BBB: intrauterine fetal death, male-mediated teratogenicity, pregnancy
t/f. male and females need to practice contraception while on vismodegib.
true
how long do restrictions of blood donation last for after tx with vismodegib?
7 months
other common ADEs of vismodegib?
Alopecia most common
GI toxicities, weight loss, fatigue
Category D pregancy
T/F. SCC does not involve drugs in initial therapy and there are targeted tx for this cancer.
false.
True - no drugs at initial tx
False - no targeted therapy
most common standard chemo drug used for tx in SCC?
cisplatin
Aldesleukin MOA?
IL-2 receptor agonist. binds to IL-2 receptor surface–> proliferation of B and T cells, monocytes, macrophages, and CTLs inlcuding NK cells
Admin for aldesleukin?
IV or SC
BBW for which conditions and using aldesleukin?
CNS - diminshed mental status, speech difficulties, corcial blindness, limb or gait ataxia, hallucinations, agitations
cardiac - hypotension, S-TACH, peripheral vasodilation, SVT
pulmonary disease- dyspnea, pulmonary congesion, rales, rhonchi
except for BBW, contradindicated in which other diseases?
renal or hepatic disease, and/or organ translplant recipeint
aldesleukin BBW for which side effect?
capillary leak syndrome (causes renal disease)
aldesleukin has significant ADEs at every organ system. Which pts can it be given to?
patients with normal cardiac and pulmonary function as determined by thallium stress testing and PFTs.
interferon MOA?
IV or SC administered immunomodulator; acts like endogenous interferon
BBW for interferon use in which 3 conditions?
autoimmune disease
cardiac disease
depression - may increase risk of suicidal ideation
also infection (no BBW)
most common ADE for interferon?
flu, flu-like symptoms (fever, fatigue)
alson: neutropenia, leukopenia, anemia, alopecia
elevated hepatic enzymes(routine LFTs required)
cough and dyspnea(pulmonary infiltrates, pneumonitis, and pneumonia)
Ipilimumab MOA?
CTLA4 recombinant antibody–> bolsters antitumor response of immune system
CTLA4 is a negative regulator of T-cell activation
Ipilimumab ADE?
severe and fatal immune-mediated adverse reaction due to T-cell activation and proliferation
dermatitis including toxic epidermal necrolysis (amonst most common severe immune rxns)
BBW for ipillimumab posted for many ADEs such as____?
adrenal insufficiency, Guillain-Barre syndrome, hepatitis, hyperthyroidism, hypopituitarism, hypothryoidism, mayasthenia gravis, peripheral neuropathy, pregnancy, serious rash
most common ADEs of ipilimumab?
tiredness, rash diarrhea
sorafenib MOA?
oral multi-kinase inhibitor (VEGF, PDGFR, KIT, raf kinase)
how is sorafenib metabolized?
hepatic metabolism - hepatitis elevated LFTs?
some ADEs of sorafenib?
most common: hand and foot syndrome, rash/desquamation, anemia
others: BM suppression, neutropenia–> use CBCs to monitor
increased risk of bleeding(possbily fatal) in GI, respiratory system, and brain
is sorafenib safe to use during pregnancy?
NO!!! category D
trametinib MOA
oral reversible MEK inhibitor for patients with BRAF V600E or V600K mutations. (not for pts who have previously received BRAF inhibitors)
most severe ADE of trametinib
rapid onset of skin toxicity(dermatitis, erythema, hand-foot sydrome); severe in 12% of patients
what are other ADEs of trametinib?
GI toxicity: diarrhea, stomatitis, anemia
decreased LVEF, HTN, hemorrhage
rarely: cardiomyopathy, interstitial lung disease, RETINAL PIGMENT EPITHELIAL DETACHMENT
MOA of vemurafenib?
oral inhibitor of mutated BRAF, including BRAF V600E
vemurafenib: is genotyping required? which type of tumors can it not be used in? how does resistance develop?
genotyping required
not be used in wild type tumors
resistance via alternate pathway activation
how is vemurafenib metabolized?
hepatic metabolism: PGP and CYP interactions possible, elevated serum creatinine –> LFTs required
ADEsof vemurafenib?
QT prolongation and TP–> LFTs required
increased photosensitivy–>avoid sunlight
cutaneous SCC in 1/4th patients (perform regular dermatologic examinations)
SEVERE dermatologic reactions possible(SJS) possible
which ADE does vemurafenib have in common with trametinib?
both cause opthalmologic issues
vemurafenib ADEs: uveitis, iritis, retinal vein occlusion
drugs with pregnancy category C status?
Aldesleukin, ipilimumab,
pregnancy category D status?
sorafenib, trametinib, vemurafenib
carmustine MOA?
both alkylation and carbamoylation of amino acids
cisplatin MOA?
forms DNA intrastrand crosslinks and adducts
cyclophosphamide MOA?
pro-drug of active alkylating moiety
dacarbazine MOA?
pro-drug of active alkylating moiety
dactinomycin MOA?
DNA intercalator
docetaxel MOA?
microtubule stabilizer; inhibits depolymerization
doxorubicin MOA?
intercalator, free radical generator, topoi II inhibitor
fluorouracil MOA?
thymidylate synthase(TS) inhibitor; interferes with RNA&RNA synthesis/function
lomustine MOA?
alkylating agent
methotrexate MOA?
DHFR inhibitor
vinblastine MOA?
microtubule formation inhibitor
dose limitation and routine care of cisplatin?
renal tubular damage and failure; myelosuppression; associated with development of secondary malignancies
dose limitation and routine care of docetaxel?
neutropenia; associated with development of secondary malignancies
all the following drugs have which dose limitation and routine care.
carmustine, cyclophosphamide, dactinomycin, doxorubicin,lomustine, methotrexate
myelosuppression and development of secondary malingancies
all of the following drugs have which dose limitation and routine care?
dacarbazine, fluorouracil, vinblastine
myelosuppresion
routine care: CBCs
what is actinic keratosis?
non-invasive lesion in sun-exposed skin (early epithelial transformation that is extremely unlikely to progress to SCC (1/1000 per annum)
diclofenac MOA?
an NSAID. inhibitor of inflammatory mediators including, PGE2.
diclofenac ADE?
Adverse reactions include itchy rash, dry skin, and skin peeling and redness
trichloroacetic acid MOA?
acetic acid; rapidly penetrates and cauterize skin, keratin, and otehr tissue
ADE of trichloroacetic acid?
burning, inflammation and localized tenderness
