RENAL CANCER PHARM

Question 1

what is the purpose of drugs in renal cancer

Answer 1

adjunctive therapy with surgery/radiation

alsowhere medical circumstances prevent surgery

Question 2

what are the common sites for metastatic growth

Answer 2

lymph nodes (most common)
lung, liver, bone (destructive lesions)
adrenal gland, Brain
opposite kidney
subq skin nodules

Question 3

Carboplatin MOA

Answer 3

platinum alkylating agent, forms DNA cross-links, resulting in inhibition of DNA synthesis and function

Question 4

cyclophosphamide MOA

Answer 4

alkylating agent, forms DNA cross-links resulting in inhibition of DNA synthesis and function

Question 5

doxorubicin MOA

Answer 5

anthracycline, oxygen free radicals bind to DNA causing strand breakage; inhibits topo II; intercalates DNA

Question 6

dactinomycin MOA

Answer 6

antineoplastic action may involve binding to DNA by intercalation between base pairs and inhibition of DNA-dependent RNA synthesis

Question 7

etoposide, MOA

Answer 7

Podophyllotoxins, inhibits topoisomerase II, resulting in DNA damage

Question 8

ifosfamide MOA

Answer 8

alkylating agent, nitrogen mustard, forms DNA cross links resulting in inhibition of DNA synthesis and function

Question 9

vincristine MOA

Answer 9

Vinca alkaloids, inhibits microtubule assembly, halts mitosis

Question 10

Aldesleukin; IL-2 MOA

Answer 10

Activates IL-2 receptors on t, B, and NK cells

Question 11

Bevacizumab MOA

Answer 11

VEGF inhibitor RESULTING IN INHIBITION OF TUMOR VASCULARIZATION

Question 12

Everolimus MOA

Answer 12

mTOR inhibitor, complex prevents protein synthesis and cell proliferation

Question 13

IFN-alpha MOA

Answer 13

antitumoral
direct antiproliferative effect on the tumor cell
induction of a host response to the tumor

also exert a cytostatic effect on tumor cells, slowing the rate of cell prliferation until cell survival is threatened

Question 14

Pazopanib MOA

Answer 14

VEGF tyrosine kinase inhibitor

Question 15

sorafenib MOA

Answer 15

VEGF tyrosine kinase inhibitors

Question 16

sunitinib MOA

Answer 16

VEGF tyrosine kinase inhibitors

Question 17

temsirolimus MOA

Answer 17

mTOR inhibitor

Question 18

carboplatin toxicity

Answer 18

myelosuppression; infection susceptibility

Question 19

cyclophosphamide toxicity

Answer 19

myelosuppression; hemorrhagic cystitits-MESNA

Question 20

doxorubicin toxicity

Answer 20

bone marrow suppression; acute and chronic cardiotoxicity

Question 21

dactinomycin toxicity

Answer 21

myelosuppression; hepatic dysfunction; infection susceptibility

Question 22

etoposide toxicity

Answer 22

hematologic toxicity; BP instability

Question 23

Ifosfamide toxicity

Answer 23

bone marrow suppression; hemorrhagic cystitits-MESNA

Question 24

VINCRISTINE toxicity

Answer 24

neurotoxicity; bilateral sensory stocking glove pattern

Question 25

rapamycins are what 2 drugs

Answer 25

temsirolimus and everolimus (mTOR inhibitors)

Question 26

what are the 3 main functions of the rapamycins

Answer 26

immunosuppressant effects inhibition of cell-cycle prog. and angiogenesis promotion of apoptosis

Question 27

Rapamycins bind to ____________ and inhibit mTORC1

Answer 27

FKBP12

Question 28

what drug prolongs survival and delays disease progression in pts with advanced and poor/intermediate risk renal cancer as compared to standard IFN-alpha treatement

Answer 28

temsirolimus

Question 29

what drug as compared to placebo, prolongs survival in pts who had failed initial treatment with anti-angiogenic drugs

Answer 29

everolimus

Question 30

temsirolimus is meabolized to what

Answer 30

sirolimus (daily oral drug)

Question 31

both temsirolimus and sirolimus are ___________substrates

Answer 31

CYP3A4

Question 32

Prominent side-effects of temsirolimus and sirolimus

Answer 32

mild maculopapular rash mucositis anemia fatigue (about 30-50% of pts) RAP MY MUFFIN A FAT-ONE

Question 33

the VEGF TK inibitors are oral drugs that are metabolized by __________-

Answer 33

CYP3A4

Question 34

what are some sunitinib specific adverse effects

Answer 34

``` fatigue hypothyroidism bone marrow suppression CHF (often with HTN) hand food syndrome ``` (SOME FAT HYPE BONES CAUSE HELL)

Question 35

what are some pazopanib specific effects

Answer 35

hepatic disease: severe and fatal hepatotoxicity hyperbilirubinemia, especially in Gilbert's syndrome

Question 36

the VEGF TK inhibitors inhibit also inhibit

Answer 36

2 other TK

Question 37

main safety concerns with bevacizumab include:

Answer 37

``` hypertension increased incidence of arterial thromboembolic events wound healing complications GI perforations proteinuria FATIGUE ```

Question 38

what are some adverse effects of aldesleukin; IL-2

Answer 38

capillary leak syndrome (extravasation of plasma proteins and fluid into the extravascular space leading to a loss of vascular tone) decreased MAP and decreased organ perfusion

Question 39

what are some adverse effects of IFN-alpha

Answer 39

neuropsychiatric events, suicide, depression, relapse drug addiction