Pharm: Drugs for skin cancer

Question 1

Which conventional chemo drugs are used for basal cell carinoma?

Answer 1

Cisplatin, cyclophosphamide (others not on focus list)

Question 2

Which targeted drugs are used for BCC?

Answer 2

Imiquimod, vismodegib

Question 3

Which drugs are used for squamous cell carcinoma?

Answer 3

Cisplatin

Question 4

Which conventional chemo drugs are used for melanoma?

Answer 4

Carmustine, dacarbazine, dactinomycin (others not on focus list)

Question 5

Which non-conventional chemo drugs are used for melanoma?

Answer 5

Immunotherapy: aldesleukin, interferon, ipilimumab
Targeted: sorafenib, trametinib, vemurafenib

Question 6

Which drugs are used for actinic keratosis?

Answer 6

Conventional: fluorouracil (not on focus list)

Non-conventional: imiquimod, trichloroacetic acid (and diclofenac, but not on focus list)

Question 7

Which drugs can be applied topically for BCC?

Answer 7

Imiquimod, (fluorouracil not on focus list)

Question 8

Which pathway is involved with BCC?

Answer 8

Hedgehog pathway (HH, PTCH, SMO, GLI)

Question 9

Imiquimod pregnancy category?

Answer 9

Cat. C

Question 10

Vismodegib pregnancy category?

Answer 10

Cat. D

Question 11

Imiquimod MOA

Answer 11

Big picture: activates immune response.

Activates TLR 7 and 8, blocks adenosine receptor, activates NF-κB (upregulates TNF, ILs)

Question 12

Imiquimod adverse effects

Answer 12

Local irriation (to inactive ingredients: paraben, benzyl alcohol), photosensitivity (avoid direct sunlight), may compromise birth control (condom, diaphragm) when used to treat HPV

Question 13

Imiquimod indications

Answer 13

BCC, actinic keratosis, HPV

Question 14

Imiquimod administration

Answer 14

Topical

Question 15

Vismodegib MOA

Answer 15

Directly inhibits SMO

Question 16

Vismodegib administration

Answer 16

Oral

Question 17

Vismodegib distribution

Answer 17

Includes semen (hence male mediated teratogenicity)

Question 18

Vismodegib metabolism, excretion

Answer 18

Hepatic: extensive metabolism (it’s a lipophilic molecule)

Excreted in bile

Question 19

Vismodegib adverse effects

Answer 19

Due to blocking SMO:
Severe birth defects
Male-mediated teratogenicity
Intrauterine fetal death

Other:
Alopecia (most common AE)
GI: N/V/D
Wt loss
Fatigue

Question 20

What must a woman taking vismodegib do?

Answer 20

Be on the most effective birth control possible, and continue for at least 7 months after drug therapy has stopped

Question 21

What must you tell a man taking vismodegib?

Answer 21

Inform him about male-mediated teratogenicity

Question 22

What is the primary treatment for SCC?

Answer 22

Surgery (with or without radiation)

Question 23

What drugs can be used for SCC?

Answer 23

No standard regimen, but cisplatin appears to be most effective

Question 24

What are the advantages/disadvantages of using conventional chemo drugs for melanoma?

Answer 24

Poor response rate, better side-effect profile

Question 25

What are the advantages/disadvantages of using immunotherapy drugs for melanoma?

Answer 25

Better response rate, bad side effect profile

Question 26

What are the immunotherapy drugs that can be used for melanoma?

Answer 26

Aldesleukin, interferon, ipilimumab

Question 27

Aldesleukin MOA

Answer 27

Binds to IL-2 receptor: prolif. and differentiation of macrophages, monocytes, T & B cells, NK cells

Question 28

Aldesleukin adverse effects

Answer 28

Capillary leak syndrome (due to activation of NK cells) CV: vasodilation, hypotension, sinus tachycardia, supraventricular arrhythmias CNS: Diminished mental status, speech difficulties, limb/gait ataxia, cortical blindness, hallucinations, agitation Pulmonary: cough, dyspnea, rales, rhonchi Renal: renal failure due to capillary leak syndrome Liver: hepatic failure (due to cap. leak syndrome)

Question 29

Aldesleukin contraindications:

Answer 29

CNS, cardiac, pulm, renal, hepatic disease. | Organ transplant recipient (will cause rejection)

Question 30

Who can recieve aldesleukin therapy?

Answer 30

Only stable patients: very bad side effect profile.

Question 31

What should you monitor with aldesleukin therapy?

Answer 31

Baseline organ function tests, daily CXR

Question 32

Interferon MOA

Answer 32

Acts like endogenous interferon: binds to IFNAR, signals through JAK/STAT pathway, leads to transcription of >300 genes

Question 33

Interferon Administration

Answer 33

IV or SC

Question 34

Aldesleukin administration

Answer 34

IV or SC

Question 35

Interferon adverse effects

Answer 35

Most common: flu, flu-like illness Worsening of preexisting infection, blood toxicity, alopecia, elevated LFTs. Pulmonary: cough/dyspnea, pulm. infiltrates, pneumonitis, pneumonia

Question 36

Interfereon BBW

Answer 36

Autoimmune disease, cardiac disease, depression

Question 37

What do you have to monitor with interferon?

Answer 37

CBC, CXR, LFTs, EKG

Question 38

Ipilimumab MOA

Answer 38

Big picture: leads to cytotoxic T cell activation. Anti-CTLA4 mAb: binds to CTLA4, prevents it from interacting with B7 (aka CD80/86); so, it inhibits an inhibitor of T cell activation.

Question 39

Ipilimumab Admin

Answer 39

IV

Question 40

Ipilimumab adverse effects

Answer 40

Most common: fatigue, diarrhea, itching, dermatitis (range from mild to toxic epidermal necrolysis

Question 41

Ipilimumab BBWs

Answer 41

Very many

Question 42

Sorafenib MOA

Answer 42

Multi-TKI (inhibits VEGF-R, PDGFR, KIT, Raf kinase)

Question 43

Sorafenib administration

Answer 43

Oral

Question 44

Sorafenib metabolism

Answer 44

Hepatic (causes LFTs)

Question 45

Sorafenib Adverse effects

Answer 45

Most common: rash/desquamation (can be severe), anemia, hand/foot syndrome. Other: Hepatic dysfunction (due to hepatic metabolism) Rare: hemorrhage (inhibition of VEGF-R) in GI, respiratory and CNS reported

Question 46

How effective is sorafenib in the treatment of melanoma?

Answer 46

Combined with dacarbazine, it increases progression-free survival, but not overall survival

Question 47

Sorafenib pregnancy category?

Answer 47

Cat. D

Question 48

What is the recommended regimen for sorafenib?

Answer 48

Dacarbazine IV on day 1 | Daily sorafenib PO x 21 days

Question 49

Trametinib MOA

Answer 49

Reversible MEK inhibitor (requires genetic testing of tumor)

Question 50

Who can't use trametinib?

Answer 50

People with previous anti-BRAF treatment

Question 51

Trametinib admin

Answer 51

oral

Question 52

Trametinib adverse effects

Answer 52

Most common: elevated LFTs, dermatitis, erythema, hand/foot syndrome, diarrhea. Other: GI: stomatitis, anemia, decreased LVEF, HTN, hemorrhage. Rare: cardiomyopathy, interstitial lung disease, retinal pigment epithelial detachment

Question 53

What do you have to monitor with trametinib therapy?

Answer 53

Ejection fraction, CBC, LFTs

Question 54

Vemurafenib MOA

Answer 54

Inhibits BRAF (must do genetic testing to confirm V600E mutation)

Question 55

Vemurafenib resistance mechanisms

Answer 55

Alternative signaling pathway

Question 56

Vemurafenib admin

Answer 56

oral

Question 57

Vemurafenib metabolism

Answer 57

Hepatic: P-gp and CYP interactions possible

Question 58

Vemurafenib adverse effects

Answer 58

Common: arthralgia, fatigue, rash, photosensitivity, alopecia, N/D. Serious: renal dysfunction, liver toxicity, QT prolong/TdP, cutaneous SCC (in 25% of patients), Stevens-Johnson syndrome, eyes: uveitis, iritis, retinal vein occlusion

Question 59

What do you have to monitor with vemurafenib?

Answer 59

LFTs, EKG, electrolytes, do a regular derm exam

Question 60

What drugs can be used to treat actinic keratosis?

Answer 60

Topical fluorouracil, imiquimod, diclofenac, trichloroacetic acid