Renal Carcinoma Rx

Question 1

Principal therapy for curing renal cancer?

Answer 1

Surgical excision

Question 2

Indications for chemotherapy in renal cancer?

Answer 2

advanced stage/grade, metastasis, adjunctive therapy with surgery/radiation, medical circumstances that exclude surgery

Question 3

Metastatic sites?

Answer 3

Lymph nodes (most common), Liver/Lungs/Bone (worst prognosis), adrenals, brain, contralateral kidney, subQ skin nodules

Question 4

What is a Wilm’s tumor?

Answer 4

Nephroblastoma seen in children, usually ages 3-4

Question 5

Genetic condition significant in Clear cell renal cell carcinoma?

Answer 5

von Hippel-Lindau gene mutation

Question 6

Pathophysiology of von Hippel-Lindau?

Answer 6

No pVHL synthesis–> excessive HIF–> translocates to the nucleus and up-regulates VEGF

Question 7

Bevacizumab?

Answer 7

anti-VEGF monoclonal antibody

Question 8

Axitinib MoA?

Answer 8

blocks VEGFR and PDGFR tyrosine kinase

Question 9

Pazopanib MoA?

Answer 9

blocks VEGFR, PDGFR, FGFR, and c-Kit

Question 10

Sunitinib MoA?

Answer 10

blocks VEGFR tyrosine kinase

Question 11

Sorafenib MoA?

Answer 11

blocks VEGFR, PDGFR, KIT, and Raf tyrosine kinsaes

Question 12

Everolimus and Temsirolimus MoA?

Answer 12

blocks mTOR activity

Question 13

Effects of Everolimus and Temsirolimus?

Answer 13

Immunosuppresant, Inhibition of cell-cycle progression and angiogenesis, and promotion of apoptosis

Question 14

Resistance to Everolimus and Temsirolimus?

Answer 14

Incompletely understood, but might arise through the action of a 2nd mTOR complex that isn’t inhibited by the drugs

Question 15

General indications of Everolimus and Temsirolimus?

Answer 15

refractory patients, or those with a poor prognosis. They prolong survival and delay disease progression

Question 16

Metabolism of Everolimus and Temsirolimus?

Answer 16

CYP3A4 (Rx-Rx interactions)

Question 17

Most common adverse drug effects seen with Everolimus and Temsirolimus?

Answer 17

mild maculopapular rash, mucositis, anemia, and fatigue (all of these are very common)

Question 18

Specific adverse drug effect seen in Everolimus?

Answer 18

Pulmonary infiltrates (stop the Rx if patient develops cough, dyspnea, or radiologic evidence of infiltrates)

Question 19

Treatment for Everolimus induced pulmonary infiltrates?

Answer 19

Stop the Rx, treat the patient with prednisone (speeds up resolution)

Question 20

The tyrosine kinase inhibitors?

Answer 20

Axitinib, Sunitinib, Sorafenib, Pazopanib

Question 21

Primary MoA of the TKIs?

Answer 21

inhibit VEGFR tyrosine kinases

Question 22

Metabolism of TKIs?

Answer 22

CYP3A4 (Rx-Rx interactions)

Question 23

General adverse effects seen with TKIs?

Answer 23

Cardiovascular issues (VEGFR inhibition); HTN (normally requires acute management), QT prolongation, thromboembolism, hemorrhagic events, blood dyscrasias

Question 24

Drugs producing QT prolongation?

Answer 24

Pazopanib and Sorafenib

Question 25

Drugs producing hepatic failure?

Answer 25

Pazopanib and sunitinib (black box warning, know this)

Question 26

Drugs producing Stevens Johnson Syndrome (hypersensitivity)?

Answer 26

Sorafenib and Sunitinib

Question 27

Other general adverse effects of TKIs?

Answer 27

Proteinuria, Endocrine dysfunction (Thyroid/Adrenals/Blood glucose), and elevated hepatic enzymes

Question 28

Bevacizumab adverse effects?

Answer 28

Thromoboembolic events, hypertension, CHF, proteinuria, and blood dyscrasias

Question 29

Black box warning for Bevacizumab?

Answer 29

Hemorrhage, GI perforations, and Wound healing complications

Question 30

IL-2 drug?

Answer 30

Aldesleukin

Question 31

Administration of Aldesleukin (IL-2)?

Answer 31

IV (in hospital)

Question 32

Syndrome of adverse effects seen with Aldesleukin?

Answer 32

Capillary Leak Syndrome (Hypotension, low PVR, tachycardia, hematologic toxicity, pulmonary edema, renal toxicity)

Question 33

Common complication of Aldesleukin therapy?

Answer 33

Development of sepsis; can occur in 70% of patients without abx therapy

Question 34

Low dose infusion of IL-2?

Answer 34

possibly leads to selective expansion of a subset of NK cells that have a high affinity IL-2 receptor

Question 35

MoA of Interferon-alpha 2b therapy?

Answer 35

upregulation of genes for antiviral, anti-proliferative, and anti-tumor activity

Question 36

Administration of Interferon-alpha 2b?

Answer 36

SubQ, 3 times weekly

Question 37

Black Box warning for Interferon-alpha 2b?

Answer 37

Neuropsychiatric, autoimmune, ischemic, and infectious disorders

Question 38

Most common adverse effects of Interferon-alpha 2b?

Answer 38

Fatigue, Fever, Flu-like symptoms, leukopenia, and neutropenia?

Question 39

Administration of TKIs?

Answer 39

Oral

Question 40

Administration of Temsirolimus?

Answer 40

IV- weekly

Question 41

Administration of Everolimus?

Answer 41

Oral- daily