Pharm-Skin Cancer Flashcards
Carmustine indication
melanoma
Cisplatin indication
Basal, squamous
Cyclophosphamide indication
basal
Cyclophosphamide indication
basal
Dacarbazine indication
melanoma
Dactinomycin indication
melanoma
docetaxel indication
melanoma
Doxorubicin indication
basal
Fluorouracil indication
basal, actinic keratosis
lomustine indication
melanoma
MTX indication
basal
Vinblastine indication
Basal, melanoma
Aldesleukin indication
melanoma
diclofenac indication
ak
imiquimod indication
basal, ak
interferon indication
melanoma
ipilimumab indication
melanoma
sorefenib indication
melanoma
trametinib indication
melanoma
trichloroacetic acid indication
ak
vemurafenib indication
melanoma
vismodegib indication
basal
Which drug is most likely to be used against SCC?
Cisplatin
Most drugs are used for these cancers
BCC and melanoma
Most popular chemo drug for SCC?
cisplatin
Most popular chemo drugs for melanoma?
D drugs (exc doxo)
Describe the treatment algorithm of basal cell carcinoma
1) Topical 5-FU or Imiquimod
2) Cisplatin chemo for metastases and Vismodegib (HH) targeted therapy
Imiquimod MOA
TLR7 and 8 activator and adenosine blockage that upregulates Nf-kB -> cytokine up regulation (immunostimulant)
ALSO HH pathway repression by modulating “GLI”
Imiquimod is also used for these non-cancers
AK, HPV
Imiquimod route
topical, limited systemization
Imiquimod AEs
Photosensitivity, compromised birth control when used for HPV
HH pathway inhibitors target this protein
Smoothened (SMO)
HH pathway goes awry most commonly in this skin cancer
Basal
Vismodegib MOA
SMO inhibitor
Vismodegib AEs
3 BLACK BOX WARNINGS:
Intrauterine fetal death
Male-mediated teratogenicity
Pregnancy
alopecia, GI common
Which drug does NOT act as a teratogen?
Imiquimod
Describe the treatment for squamous cell carcinoma?
Surgery/radiation, not drugs; Cisplatin-based regimen for metastatic/advanced disease
Describe the different drug modalities and their comparative effectivness in treating melanoma
Conventional chemo - bad ~7%
Immunotherapy - better but very toxic
Signal transduc inhibitors - best, BRAF mut target
What are the signal transduction inhibitors used in melanoma?
Sorafenib, trametinib, vemurafenib
Aldesleukin MOA
IL-2 receptor binder -> proliferation of B and T cells, monos, macros, and CTLs inc NK
Aldesleukin black box warnings
CNS, cardiac, pulmonary disease
IL-2 activation drawback
Also stimulates Tregs which diminish benefits
Can cause capillary leak syndrome
IFN-alpha MOA
RTK activation->antiviral, antiproliferative, cytokine induction, HLA expression…
IFN-alpha C/Is bbw
Autoimmune, cardiac disease, depression (suicidal ideations)
IFN common AEs
Flu-like, leukopenia, anemia
Liver issues
Pulmonary issues
Ipilimumab MOA
Stimulate T cell function by binding CTLA4, a T cell repressor (cytotoxic lymphocyte-associated antigen)
It’s an “indirect” action on melanoma?
Ipilimumab serious AEs
Severe immune-mediated AEs inc dermatitis and toxic necrolysis;
MANY BBWS: adrenal, hepatitis, hyperthryoid, hypopituitary, hypoT, MG, peri neurop, preg, rash
Ipilimumab common AEs
Fatigue, diarrhea, itching, rash
Sorafenib MOA
Multikinase inhibitor:
VEGF, PDGFR, KIT, RAFK
Blocks both 1)proliferative and 2)angiogenic signaling
Sorafenib AEs
Severe rash, hepatic dys, hematologic
Common: hand/foot, anemia, rash
Prego - cat D
fatal bleeding possible
Combining these two drugs demonstrated increased progress-free survival in melanoma patients but not overall survival
Dacarbazine plus sorafenib
Which drugs require genotyping?
Trametinib and vemurafenib (for BRAF, for melanoma)
Trametinib MOA
MEK inhibitor for patients with BRAF V600E or V600K mutations
Trametinib AEs
Severe skin toxicity in 12%
GI, diarrhea
Dec LVEF!, HTN, Hemorrhage
Rarely: cardiomyopathy, ILD, EYE stuff
Both of these drugs block MEK
Trametinib and Vemurafenib
How does resistance develop to BRAF targeted drugs?
Proliferative signaling by a parallel, unaffected pathway
E.g., RAS-driven proliferation
Vemurafenib Aes
Inc risk of cutaneous SCC
Liver, cardiac, EYE
Most common: arthralgia, fatigue, rash, photosensitivity
Describe the common toxicity profile for BRAF inhibitors
RASH Liver Heart Eye 2ndary maligs
Carmustine MOA
Alkylation and carbamoylation of amino acids
Dactinomycin MOA
DNA intercalator
Lomustine MOA
alkylating agent
Carmustine AEs
myelosuppression
Dacarbazine AE
myelosuppression
Dactinomycin AE
Myelosuppression
Which drugs are used for actinic keratosis?
5-FU, Imiquimod
Diclofenac - PGE2 inhibitor
Tri-Chlor - peel
all are topical so no systemic toxicity
Diclofenac MOA
Inflammation inhib inc PGE2
Diclofenac AEs
Itchy rash, dry skin, peeling, redness
Trichlor MOA
Chemical peel that penetrates and cauterizes skin and keratin
Trichlor AEs
burning, inflammation, tenderness
