656 - Skin Cancer (Set 3)

Front 1

What is the mechanism of action for dacarbazine?

Back 1

Alkalation of DNA leading to double strand breaks and apoptosis.

Front 2

What are the indications for dacarbazine?

Back 2

Metastatic melanoma & Second line therapy for Hodgkin's when used in combination.

Front 3

Describe dosing for dacarbazine.

Back 3

150 mg/m^2 IV days 1 through 5 every 3 weeks

Front 4

Describe dose adjustments for dacarbazine.

Back 4

Adjust for renal impariment. CrCL 46-60: administer 80% of dose. CrCL 31-45: administer 75% of dose. CrCL < 30: administer 70% of dose.

Front 5

Describe the efficacy of dacarbazine for the treatment of metastatic melanoma.

Back 5

Low response rates. No overall survival benefit.

Front 6

What are the common adverse effects of dacarbazine?

Back 6

Nausea/Vomiting, Alopecia, Flu-Like Symptoms, Headache

Front 7

What rare but serious adverse effects are associated with dacarbazine?

Back 7

Photosensitivity, Myelosuppression, Hepatotoxicity, & Seizure

Front 8

What drug interactions are associated with dacarbazine?

Back 8

Dacarbazine is a substrate of CYP1A2 and 2E1, so inducers or inhibitors of these enzymes alter dacarbazine metabolism.

Front 9

What monitoring parameters are recommended for dacarbazine?

Back 9

CBC with differential, LFTs, & Tumor Response

Front 10

What counseling pearls are advised with dacarbazine?

Back 10

This medication may cause hair loss, nausea, vomiting, and flu-like symptoms, such as fever and fatigue. Immediately report easy bruising or bleeding, yellowing of eyes or skin, change in color of urine, or blackened stool.

Front 11

What is the mechanism of action for ipilimumab?

Back 11

Monoclonal antibody. Binds to cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), which down regulates T-cell activation pathways (by binding to it, it prevents CTLA-4 mediated immunosuppression). This enhances T-cell activation and proliferation.

Front 12

What are the indications for ipilimumab?

Back 12

Unresectable or metastatic melanoma.

Front 13

Describe dosing of ipilimumab.

Back 13

3 mg/kg IV over 90 minutes every 3 weeks.

Front 14

What dosage adjustments are required for ipilimumab.

Back 14

Hold if hepatotoxicity is observed during treatment.

Front 15

Describe the efficacy of ipilimumab.

Back 15

Less than 20% overall response rate. Of those who respond, the 3-year survival rate is 20.8%.

Front 16

What are the common adverse effects of ipilimumab?

Back 16

Pruritis, Rash, GI upset, & Fatigue

Front 17

What rare but serious adverse effects are associated with ipilimumab?

Back 17

Enterocolitis, Hepatotoxicity, Infections, Renal Failure, Hypothyroidism, & Neuropathy

Front 18

What drug interactions are associated with ipilimumab?

Back 18

No formal drug interaction studies have been conducted.

Front 19

What monitoring parameters are recommended for ipilimumab?

Back 19

LFTs, Thyroid Function Tests, & Tumor Response

Front 20

What counseling pearls are advised for ipilimumab?

Back 20

Report immediately if experiencing abdominal pain and blood or mucous in stool or diarrhea. Report immediately if feeling bilateral weakness, sensory changes, or paresthesias.

Front 21

For what reason was ipilimumab placed in a REMS program?

Back 21

T-cell activation and proliferation can result in severe and fatal immune-mediated adverse reactions, such as enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. When they occur, these reactions typically present during treatment, but they may occur weeks to months after discontinuation.

Front 22

What recommendations are associated with the ipilimumab REMS program?

Back 22

Assess patients for signs and symptoms of enterocolitis, dematitis, neuropathy, and endocrinopathy before each dose. If any are observed, permanently discontinue ipilimumab and intitate high dose corticosteroid therapy.

Front 23

How does ipilimumab plus dacarbazine compare with placebo plus dacarbazine in the treatment of metastatic melanoma with respect to overall survival and median duration of response?

Back 23

Overall survival was 11.2 months with ipilimumab vs. 9.1 months with placebo. Median duration of response was 19.3 months with ipilimumab vs. 8.1 months with placebo.

Front 24

What is the mechanism of action for vemurafenib?

Back 24

BRAF kinase inhibitor. Blocks BRAF^V600E mutation, which prevents cellular proliferation in melanoma cells. NOT effective in wild-type BRAF mutation.

Front 25

What are the indications for vemurafenib?

Back 25

Unresectable or metastatic melanoma with BRAF^V600E mutation (about 50 to 60% of melanomas).

Front 26

Describe dosing of vemurafenib for metastatic melanoma.

Back 26

960 mg PO BID

Front 27

What dosage adjustments are required for vemurafenib?

Back 27

No adjustments necessary.

Front 28

Describe the efficacy of vemurafenib for the treatment of metastatic melanoma.

Back 28

40 to 50% overall response rate. Duration of response = 5 to 6 months.

Front 29

What are the common adverse effects of vemurafenib?

Back 29

Alopecia, Photosensitivity, Rash, Nausea, Arthralgia, & Fatigue

Front 30

What rare but serious adverse effects are associated with vemurafenib?

Back 30

Prolonged QT Interval, Hand-Food Syndrome, Squamous Cell Carcinoma, & Vision Changes

Front 31

What drug interactions are associated with vemurafenib?

Back 31

Vemurafenib is a substrate of CYP3A4, so inducers and inhibitors alter vemurafenib metabolism. Vemurafenib is an inducer of CYP3A4 and an inhibitor of CYP1A2 and 2D6.

Front 32

What monitoring parameters are recommended for vemurafenib?

Back 32

LFTs & Electrocardiogram

Front 33

What counseling pearls are advised with vemurafenib?

Back 33

Pills should be taken whole, do not crush or break. Educate on routine skin exams and sun protection. Report immediately any changes in vision.