Drugs to treat skin cancer

Question 1

What CTX can be given for basal cell carcinoma?

Answer 1

cisplatin; cyclophosphamide; imiquimod; vismodegib

Question 2

What is the CTX agent for squamous cell carcinoma?

Answer 2

cisplatin

Question 3

What CTX can be given for melanoma?

Answer 3

carmustine; dacarbazine; docetaxel; aldesluekin; interferon; ipilimumab; sorafenib; trametinib; vemurafenib

Question 4

What CTX can be given for actinic keratosis?

Answer 4

imiquimod; trichloroacetic acid

Question 5

Conventional and targeted CTX are commonly used in what diseases?

Answer 5

BCC and melanoma

Question 6

Unusual agents like an NSAID and TCA treat for what?

Answer 6

actinic keratosis

Question 7

T/F most skin cancers are cured if found and Tx begins early

Answer 7

true

Question 8

If localized BCC Tx with fluoruracil does not work or the lesion is small and in a low risk site, what is the Tx?

Answer 8

topical imiquimod

Question 9

If BCC is metastatic, what is the most effective Tx?

Answer 9

cisplatin

Question 10

If BCC is metastatic and ADEs are too risky, what is the Tx of choice?

Answer 10

Vismodegib

Question 11

What is the main MOA of imiquimod?

Answer 11

smal molecule tumor directed immune response initiator (immune stimulator)

Question 12

How does imiquimod work? (3)

Answer 12

direct activation of TLR7 and/or TLR8; involvement of adenosine receptor blockade; activation of NFkB

Question 13

What does the activation of NFkB cause?

Answer 13

upregulation of cytokines like TNFa and interleukins

Question 14

Other than BCC, what can imiquimod be used for?

Answer 14

actinic keratinosis and HPV

Question 15

How is imiquimod applied?

Answer 15

topical agent for limited systematization

Question 16

What are associated ADE with imiquimod?

Answer 16

Benzyl alcohol, paraben (components of drug) allergenic; localized skin rxn; increased photosensitivity; compromise condom and diaphragm integrity

Question 17

If imiquimod is given in high concentrations, what is the effect?

Answer 17

apoptosis due to mitochondria begin damaged leading to caspase activation and Bcl-2/Bax shift

Question 18

What is significant about hedgehog signaling?

Answer 18

body patterning and organ development but in adults is associated in tissue maintenance and repair

Question 19

BCC is linked to what pathway?

Answer 19

inappropriate reactivation of the hedgehog pathway

Question 20

What is the consequence of abberant signaling of the Hh pathway?

Answer 20

upregulation of anti-apoptotic Bcl-2, VEGF induction, angiopoietins

Question 21

What is key for the action of clinical inhibitors of Hh? What is the drug used to accomplish this?

Answer 21

act at or below level of transmembrane protein SMO=> Vismodegib

Question 22

What is the MOA of vismodegib?

Answer 22

oral SMO inhibitor

Question 23

How is vismodegib metabolized?

Answer 23

extensively via a lipophilic agent

Question 24

What are the main 3 ADEs associated with vismodegib?

Answer 24

intrauterine fetal death; male mediated teratogenicity; pregnancy and blood donating

Question 25

What is significant in using vismodegib while pregnancy is in question?

Answer 25

both male and female need contraception

Question 26

What are mild ADEs of vismodegib?

Answer 26

alopecia; GI tox (common); weight loss and fatigue

Question 27

What is the initial Tx for squamous cell carcinoma?

Answer 27

surgery and/or radiation => no drug tx

Question 28

If squamous cell carcinoma is metastatic, what is the regimen?

Answer 28

no standard but cisplatin tx is most effective

Question 29

In what 3 ways can melanoma be treated?

Answer 29

immunotherapy, signal transduction inhibitors, CTX

Question 30

What are the drugs for immunotherapy of melanoma?

Answer 30

Aldesleukin (IL-2); IFN-a-2B; Ipilmumab

Question 31

What are 3 drugs for signal tranduction inhibitors for melanoma?

Answer 31

sorafenib; trametinib; vemurafenib

Question 32

What are the best CTX agents for melanoma?

Answer 32

dacarbazine; carmustine

Question 33

What is the MOA of aldesleukin?

Answer 33

binds to cell surface IL-2 receptor

Question 34

What is the effect of aldesleukin?

Answer 34

induces proliferation and differentiation of B and T cells, monocytes, macs, and CTLs including NKs

Question 35

What is Aldesleukin contraindicated in?

Answer 35

***BBW in CNS; cardiac; pulmonary***; renal; hepatic diseases or organ transplant

Question 36

What is an ADE associated with giving aldeleukin with renal failure patients?

Answer 36

capillary leak syndrome *** BBW

Question 37

What is an IV or SC administered immnomodulator?

Answer 37

Interferon-a 2B

Question 38

When should Interferon-a 2B be used with caution?

Answer 38

*** BBW in autoimmune diseases; cardiac diseases; depression;*** infection

Question 39

What is the most common ADE in Interferon-a 2B use?

Answer 39

flu like Sx

Question 40

Interferon are associated with what pulmonary Sx?

Answer 40

cough and dyspnea; pulm infiltrates, pneumonitis, pneumonia

Question 41

What common pathway does the INF-a 2b work on?

Answer 41

JAK-STAT pathway leading to upregulation of transcriptional genes

Question 42

What is the MOA of ipilimumab?

Answer 42

CTLA-4 recombinant Ab (encourages B7 binding to CTLA-4) for T cell activation

Question 43

What reason is ipilimumab administered?

Answer 43

bolsters antitumor response of immune system

Question 44

What are the ADEs of ipilimumab associated with?

Answer 44

severe and fatal immune mediated adverse rxns due to T cell activation and proliferation

Question 45

What is a common severe ADE of ipilimumab?

Answer 45

dermatitis including toxic epidermal necrolysis

Question 46

What are severe ADEs associated other diseases when given ipilimumab?

Answer 46

adrenal insufficiency; diarrhea; Guillain-Barre syndrome; hepatitis; hyper/hypothyroidism; hypopituitarism; myasthenia gravis; peripheral neuropathy; pregnancy; serious rash

Question 47

What is the multi-kinase inhibitor of VEGF, PDGF-r, KIT, Raf kinase?

Answer 47

Sorafenib

Question 48

How does the metabolism of sorafenib cause problems?

Answer 48

hepatic metabolism that may elevate LFTs in patients with hepatitis

Question 49

What are the most common ADEs with sorafenib?

Answer 49

Hand and foot syndrome; rash desquamation; anemia

Question 50

Why are routine CBCs required with sorafenib Tx?

Answer 50

bone marrow suppression and neutropenia

Question 51

What is increased that could lead to death in patients?

Answer 51

increased GI, respiratory and brain bleeding

Question 52

Does sorafenib affect pregnancy?

Answer 52

yes=> birth control required

Question 53

How does sorafenib utilize the RAF/MEK/ERK pathway?

Answer 53

inhibits tumor cell proliferation by targeting the pathway at the level of RAF kinase

Question 54

How does sorafenib exert an anti-angiogenic effect?

Answer 54

targeting the receptor tyrosine kinases VEGF-R and PDGF-r and associated cascades

Question 55

What is the MOA for Trametinib?

Answer 55

oral reversible MEK inhibitor

Question 56

What type of patients is trametinib indicated for? who is not included?

Answer 56

patients with BRAF V600E or V600K mutations => cannot give to patients previously receiving BRAF inhibitors

Question 57

What are common ADEs in patients receiving trametinib?

Answer 57

skin toxicity (dermatitis, erythema, hand-foot syndrome); GI tox; Decreased LVEF; HTN; hemorrhage

Question 58

What are rare ADEs associated with trametinib?

Answer 58

cardiomyopathy; interstitial lung disease; retinal pigment epithelial detachment

Question 59

What is the MOA of vemurafenib?

Answer 59

oral inhibitor of mutated BRAF (includes BRAFV600E)

Question 60

What is required to treat with vemurafenib? why?

Answer 60

genotyping=> cannot use in wild type tumors

Question 61

Why can vemurafenib not be used in wild type tumors?

Answer 61

paradoxical ERK activation of mutated RAS-driven growth

Question 62

How does resistance occur when using vemurafenib?

Answer 62

alternative pathway activation

Question 63

vemurafenib metabolism?

Answer 63

hepatic, PGP and CYP interactions possible; elevated serum creatinine

Question 64

How does vemurafenib affect the heart? what must be done while taking it?

Answer 64

QT prolongation => electrolyte monitoring

Question 65

What cancer is increased with vemurafenib use? why?

Answer 65

cutaneous SCC=> increased photosensitivity=> must avoid sunlight

Question 66

What severe issues are associated with vemurafenib that is not as common with other drugs?

Answer 66

uveitis, iritis, retinal vein occlusion

Question 67

What are the common toxicities of BRAF/MEK inhibitors?

Answer 67

liver; heart; eye; secondary malignancies

Question 68

What do all BRAF-MEK inhibitors require?

Answer 68

BRAF genotyping

Question 69

Which drugs are considered category C drugs?

Answer 69

aldesleukin; ipilimumab; IFN-a 2b

Question 70

Which drugs are considered category D drugs?

Answer 70

sorafenib; trametinib; vemurafenib

Question 71

What is the MOA of carmustine?

Answer 71

alkylation and carbamoylation of amino acids

Question 72

What drugs are typically used topically in actinic keratosis?

Answer 72

imiquimod

Question 73

What is the dose limitation of cisplatin?

Answer 73

renal tubular damage and failure

Question 74

What is the dose limitation of docetaxel?

Answer 74

neutropenia

Question 75

What is the dose limitation of most of the other cancer drugs?

Answer 75

myelosuppression

Question 76

How does trichloroacetic acid work?

Answer 76

chemical peel that rapidly penetrates and cauterizes skin, keratin

Question 77

What are ADEs associated with trichloroacetic acid?

Answer 77

burning; inflammation; localized tenderness

Question 78

What do interferon, sorafenib and trametinib have in common?

Answer 78

blood dyscrasias

Question 79

Which targeted drug will cause bleeding in the GI, lung and brain?

Answer 79

sorafenib

Question 80

Which targeted drug will cause HTN?

Answer 80

sorafenib

Question 81

What do Trametinib and Vemurafenib have in common?

Answer 81

eye damage

Question 82

What targeted drug is associated with secondary tumors?

Answer 82

vemurafenib

Question 83

Which targeted drugs may lead to a rash?

Answer 83

imiquimod; ipilimumab; sorafenib; trametinib; vemurafenib

Question 84

Which targeted drugs are associated with the need for genetic testing?

Answer 84

trametinib and vemurafenib

Question 85

MOA for cisplatin

Answer 85

forms DNA intrastrand crosslinks and adducts

Question 86

MOA for cyclophosphamide

Answer 86

pro-drug of active alkylating moiety

Question 87

MOA for decarbazine

Answer 87

pro drug of active alkylating moiety