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BCOP > Renal cell > Flashcards

Renal cell Flashcards

1
Q

pathophysiology -3

A

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)

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2
Q

Von Hippel-Lindau gene -3

A

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)

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3
Q

pathogenesis (3pts)

A

classic is Von Hippel-Lindau dz

others genetic abnormalities also

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

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4
Q

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

WHAT IS TOC?

CAN YOU CURE?

A

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)

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5
Q

what % present with metastatic dz? -1

A

20%, incurable but may also do radical nephectomy

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6
Q

what % of tumors occur bilaterally? -1

A

1-3%, poor outcome

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7
Q

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

A

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

DO NOT GIVE IN EARLY STAGE

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8
Q

MSKCC risk factors (5pts)

IMPORTANT FOR PROGNOSIS

IMPORTANT FOR TRIAL DESIGN

A

KPS 10

high LDH >300

time from dx to systemic tx 10

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9
Q

prognosis by MSKCC risk factor (3pts)

A

median OS with IFN-alpha

0: 30mo

1-2: 14mo

3-5: 5mo

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10
Q

stage IV: summary of cytokine data -6

A

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

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11
Q

mTOR pathway (3pts)

A

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)

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12
Q

sorafenib - 2

DO YOU USE 1ST OR 2ND LINE?

A

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

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13
Q

sorafenib dose and food issues

A

400mg bid WITHOUT food

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14
Q

sunitinib dose and ADR -5

OS 26.4 vs 21.8 (p=0.051)

DO YOU USE 1ST OR 2ND LINE?

A

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)

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15
Q

pazopanib dose and food issues

A

800mg daily WITHOUT food

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16
Q

pazopanib -4

DO YOU USE 1ST OR 2ND LINE?

A

approved for 1st or 2nd line use

PFS 9.2 vs 4.2 mo with IFN

ALT elevations seen

approved 1st line

17
Q

pazopanib vs sunitinib -2

WHAT IS PREFERRED AND WHY?

A

PFS 8.4 vs 9.5 (NS)

lower rate of fatigue and HFS and inc QOL with pazo

18
Q

axitinib dose and ADR -4

A

5mg bid

rare ADR: RPLS

other ADR: 
hypothyroidism, 
hepatotox, 
HTN, 
hemorrhagic,

vegf ae’s

19
Q

axitinib vs sorafenib IN 2ND LINE -2

WHAT IS PREFERRED AND WHY?

A

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

20
Q

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

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

A

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

21
Q

everolimus dose, DA, DDI -3

A

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)

22
Q

everolimus ADR -3

REMEMBER PRIMARY CARE ISSUES

A

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

23
Q

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

A

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

24
Q

IFN +bev vs IFN -2

DO YOU USE 1ST OR 2ND LINE?

A

approved for 1st or 2nd line use

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

BCOP (32 decks)

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