renal

Question 1

pazopanib selectivity and toxicities

Answer 1

more selective to VEGF, less fatigue mucositis, more LFT abnl; better QOL compared to sunitinib

Question 2

COMPARZ trial

Answer 2

phase III pazopanib. v. sunitinib first line; 1100 pts, non-inferiority study; reached endpoint–> pazopanib 8.4mo v. 9.5mo; HR 1.047, falling within margin

Question 3

tox with pazopanib

Answer 3

LFTs

Question 4

second line therapy

Answer 4

sorafenib

Question 5

everolimus toxicities

Answer 5

infections, stomatitis, 15% non-infectious pneumonitis

Question 6

pneumonitis toxicity everolimus

Answer 6

treat with steroids

Question 7

axitinib

Answer 7

potent VEGF inhibitor, more than pazopanib; treated in second line setting versus sorafenib; PFS improved PFS 6.7v4.7mo

Question 8

sorafenib tox

Answer 8

more skin

Question 9

axitinib tox

Answer 9

diarrhea

Question 10

second line therapy

Answer 10

either axitinib or everolimus; sequence not so important

Question 11

combinations v. monotherapy

Answer 11

no benefit of combine; temsirolimus + bev–> no added benefit, more toxicity

Question 12

poor risk tx

Answer 12

temsirolimus

Question 13

poor risk factors

Answer 13

anemia, poor PS,

Question 14

interferon for renal cancer

Answer 14

improved survival compared to megace

Question 15

IL-2 for renal

Answer 15

small proportion with durable complete response, 2.5%, high tox

Question 16

cytoreductive nephrectomy- should you take primary out?

Answer 16

2 studies with improved survival with this approach: do if no brain mets and safe procedure before starting meds

Question 17

MSKCC risk groups (prognostic)

Answer 17

KPS<80, short time to need for treatment 12mo, low Hgb, high Ca, high LDH. favorable 0, 1-2 int, 3-5 poor.

Question 18

temsirolimus FDA approval

Answer 18

used for the poor risk group only

Question 19

histotypes of RCC

Answer 19

75% clear cell, 15% papillary, 5% chromophobe, 5% oncocytoma, rare others

Question 20

clear cell RCC

Answer 20

VHL mutation (70-70%), LOH (3p25), or hypermethylation

Question 21

Type 1 papillary RCC

Answer 21

c-met mutation

Question 22

Type 2 papillary RCC

Answer 22

FH mutation

Question 23

VHL gene

Answer 23

tumor supresssor that regulates angiogenesis and cell proliferation. turns off wit hypoxia–>allows HIFa–> (VEGF, PDGF, TGF/EGFR). Mutation is constitutively off

Question 24

sorafenib for RCC

Answer 24

improved PFS 5.9v 2.8mo compared to placebo, only 2% PR but 78% SD.

Question 25

sorafenib/nexavar tox

Answer 25

RASH, hand/food in high proportions.

Question 26

first line RCC

Answer 26

sunitinib (biggest trial), bev+IFN, pazopanib (smaller trial), temsiroliumus (poor risk). no comparatives with each other.

Question 27

high risk RCC first line

Answer 27

temsirolimus (better than IFN or IFN/tem), IV weekly. more SD, low ORR.

Question 28

tox, temsirolimus

Answer 28

rash, LE dema, stomatitis, hypergly, HL, thrombocytopenia, dyspnea. (borderline DM tips them over)

Question 29

sunitinib toxicity

Answer 29

fatigue is most common to require dose reduction. others include HTN, nausea, hand/food, 13% with EF cardiac function. get baseline TTE, and yearly TTE.

Question 30

pazopanib tox

Answer 30

less fatigue, hand food, stomatitis, but more liver toxicity

Question 31

pazopanib v. sunitinib (COMPARZ)

Answer 31

1100pts, NONINFERIOR. sunitinib more fatigue, count suppression. pazopanib has more LFTs, and hair color changes.

Question 32

pazopanib LFT ab

Answer 32

if prolonged, then switch to sunitinib

Question 33

everolimus versus placebo in RCC

Answer 33

approved for third line

Question 34

tox of everolimus

Answer 34

pneumonitis.

Question 35

axitinib for RCC

Answer 35

most selective for VEGF. improved PFS compared to sorafenib in 2nd line setting.

Question 36

tox of axitinib

Answer 36

diarrhea, HTN.

Question 37

when to give everolimus?

Answer 37

either second line or beyond, doesn't really matter when

Question 38

nivolumab dosing in RCC

Answer 38

phase II, Motzer: measure PFS, ORR was 20% across all arms, and durable response, most of them more than year. OS for group, 24 month OSS. now a phase III nivo versus everolimus following progression on a VEGFR.

Question 39

Birt-Hogg-Dube

Answer 39

-ch1, -Y. associated with chromophobe and oncocytoma variation. also has pulmonary nodules/hamartomas.

Question 40

hereditary papillary RCC

Answer 40

associated with c-met activating mutation, or hydratase inactivating mutation

Question 41

Stauffer syndrome

Answer 41

paraneoplastic liver failure that reverses with nephrectomy for RCC

Question 42

VHL syndrome

Answer 42

RCC, retinal angiomas, hemangioblastomas of CNS, pheochromocytomas

Question 43

VHL genetics

Answer 43

loss of VHL-->loss of ubiquitinization of HIF1a-->increased HIF1a--> increased VEGF/PDGF

Question 44

medullary carcinoma of kidney

Answer 44

associated with sickle cell

Question 45

type I papillary RCC

Answer 45

good prognosis

Question 46

type II papillary RCC

Answer 46

associated with poor prognosis

Question 47

treatment of RCC with bev

Answer 47

bev+IFN better than IFN alone; monotherapy is not tested

Question 48

first line RCC, good risk

Answer 48

pazopanib or sunitinib; pazopanib- less fatigue/hand food, thrombocytopenia, mucositis; more LFT abnl

Question 49

high risk RCC

Answer 49

only temsirolimus approved. 3 or more of the following: LDH, Hgb, Ca,

Question 50

second line good risk RCC Tx

Answer 50

axitinib OR everolimus. sorafenib worse than axitinib

Question 51

IL-2 for RCC

Answer 51

can use if good PFS and clear cell variant, in first line

Question 52

chemotherapy for RCC

Answer 52

if sarcomatoid- gem/dox; if collecting duct- gem/cis; if clear cell- gem/5-FU(or xeloda)

Question 53

treatment of mTOR-associatead pneumonitis

Answer 53

grade 1- ASx radiographic- monitor and continue; grade 2- Sx mild- hold and give steroids, then dose reduce.