Renal cell

Question 1

pathophysiology -3

Answer 1

80-85% of kidney tumors are renal cell:

• 75-85% clear cell
• 12-14% chromophilic
• 4-6% chromophobic
• others

15-20% transitional cell

wilm’s tumor (kids)

Question 2

Von Hippel-Lindau gene -3

Answer 2

tumor suppressor gene

deletion in short arm of chromosome 3p

regulates HIF (hypoxic inducable factor) which controls angiogenic processes VEGF and PDGF (goes unchecked with mutation)

Question 3

pathogenesis (3pts)

Answer 3

classic is Von Hippel-Lindau dz

others genetic abnormalities also

multiple (more than 1) genetic abnormalities associated with poor outcomes

Question 4

treatment of T1 and T2 (confined to renal parenchyma) -3

WHAT IS TOC?

CAN YOU CURE?

Answer 4

SURGERY ONLY (NEOADJ IS NOT GIVEN)

radical nephrectomy cures >80% of time,

only surgery curative,

not preferred but can do partial nephrectomy in pts for whom radical would result in permanent dialysis OR if contralateral kidney is threatened by a second disease (DM, HTN)

Question 5

what % present with metastatic dz? -1

Answer 5

20%, incurable but may also do radical nephectomy

Question 6

what % of tumors occur bilaterally? -1

Answer 6

1-3%, poor outcome

Question 7

treatment of T1 and T2 (confined to renal parenchyma) - partial nephrectomy + adjuvant -1

Answer 7

IFN-alpha WORSE than placebo: median OS 5.1 vs 7.4yrs

DO NOT GIVE IN EARLY STAGE

Question 8

MSKCC risk factors (5pts)

IMPORTANT FOR PROGNOSIS

IMPORTANT FOR TRIAL DESIGN

Answer 8

KPS 10

high LDH >300

time from dx to systemic tx 10

Question 9

prognosis by MSKCC risk factor (3pts)

Answer 9

median OS with IFN-alpha

0: 30mo

1-2: 14mo

3-5: 5mo

Question 10

stage IV: summary of cytokine data -6

Answer 10

IFN-alpha and IL-2 have ~ same RR, BUT IL-2 has more “durable” (5,6,7 yr) responses

reserve IL-2 for young with good organ function and good PS because of tox

high dose IL-2 preferred (similar to melanoma)

combo increased RR but NOT OS

removal of primary tumor followed by IFN may inc RR (not true adjuvant b/c still have met dz in rest of body)

most trials use IFN as control

Question 11

mTOR pathway (3pts)

Answer 11

leads to biosynthesis of HIF (similar to VHL) -> VEGF and PDGF

mTOR lies downstream of PI3K

CONTROLS CELL REGULATION PROCESS by regulates cell growth and cell proliferation (G1 to S phase)

Question 12

sorafenib - 2

DO YOU USE 1ST OR 2ND LINE?

Answer 12

approved for 2nd line use after IFN

RR 10 vs 2 (sig)

TTP 5.5 vs 2.8 (sig)

OS: 17.8 vs 15.2 (NS)

IN front line setting vs IFN did not show PFS benefit, because of this is 2nd line option

Question 13

sorafenib dose and food issues

Answer 13

400mg bid WITHOUT food

Question 14

sunitinib dose and ADR -5

OS 26.4 vs 21.8 (p=0.051)

DO YOU USE 1ST OR 2ND LINE?

Answer 14

APPROVED FOR 1ST LINE OR 2ND LINE

50mg daily x4wks, THEN 2 weeks OFF

rash, 
HFS, 
dry skin, 
HTN, 
diarrhea

less common: 
neutrop, 
hepatotox, 
dec LVEF, 
prolonged QT, 
hemorrhagic events

other anti-VEGF ae (proteinuria, wound healing)

Question 15

pazopanib dose and food issues

Answer 15

800mg daily WITHOUT food

Question 16

pazopanib -4

DO YOU USE 1ST OR 2ND LINE?

Answer 16

approved for 1st or 2nd line use

PFS 9.2 vs 4.2 mo with IFN

ALT elevations seen

approved 1st line

Question 17

pazopanib vs sunitinib -2

WHAT IS PREFERRED AND WHY?

Answer 17

PFS 8.4 vs 9.5 (NS)

lower rate of fatigue and HFS and inc QOL with pazo

Question 18

axitinib dose and ADR -4

Answer 18

5mg bid

rare ADR: RPLS

other ADR: 
hypothyroidism, 
hepatotox, 
HTN, 
hemorrhagic, 

vegf ae’s

Question 19

axitinib vs sorafenib IN 2ND LINE -2

WHAT IS PREFERRED AND WHY?

Answer 19

A approved for 2nd line use after IFN

A superior to S in 2nd line setting

RR 19 vs 9

PFS 6.7 vs 4.7mo

Question 20

everolimus for pts progressing after sorafenib and/or sunitinib -5

DO YOU USE 1ST OR 2ND LINE? after what tx?

Answer 20

approved for 2nd line use after TKI’s (OR THIRD LINE)

oral mTOR inhibitor

improved PFS 4.9 vs 1.9 mo

mostly stable dz

No OS benefit

Question 21

everolimus dose, DA, DDI -3

Answer 21

10mg daily, 28d cycles

reduce to 5mg if Child-Pugh class B hepatic impairment

CYP3A4 substrate (may inc in 5mg increments to 20md daily if on strong inducer)

Question 22

everolimus ADR -3

REMEMBER PRIMARY CARE ISSUES

Answer 22

common: stomatitis, rash, fatigue
rare: pneumonitis
other: hyperglycemia, hyperlipidemia, hypercholesteremia (manage these ae’s)

Question 23

temsirolimus in 1st line setting in poor risk pts (cat 1) -6

DO YOU USE 1ST OR 2ND LINE?

WHAT RISK SUBGROUP STUDIED?

REMEMBER PRIMARY CARE ISSUES

Answer 23

approved for 1st or 2nd line use

70% POOR RISK PTS (USE FOR THESE PTS)

25mg IV qweek (require diphen as premed) vs IFN

OS 10.9 vs 7.3 mo, PFS 3.8 vs 1.9 mo

combo of the TEM + IFN no benefit over temsirolimus alone

same ADR as everolimus

Question 24

IFN +bev vs IFN -2

DO YOU USE 1ST OR 2ND LINE?

Answer 24

approved for 1st or 2nd line use

PFS: 10.2 vs 5.4 mo (sig), OS: 21.3 vs 23.3 (NS)