renal Flashcards
pazopanib selectivity and toxicities
more selective to VEGF, less fatigue mucositis, more LFT abnl; better QOL compared to sunitinib
COMPARZ trial
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
tox with pazopanib
LFTs
second line therapy
sorafenib
everolimus toxicities
infections, stomatitis, 15% non-infectious pneumonitis
pneumonitis toxicity everolimus
treat with steroids
axitinib
potent VEGF inhibitor, more than pazopanib; treated in second line setting versus sorafenib; PFS improved PFS 6.7v4.7mo
sorafenib tox
more skin
axitinib tox
diarrhea
second line therapy
either axitinib or everolimus; sequence not so important
combinations v. monotherapy
no benefit of combine; temsirolimus + bev–> no added benefit, more toxicity
poor risk tx
temsirolimus
poor risk factors
anemia, poor PS,
interferon for renal cancer
improved survival compared to megace
IL-2 for renal
small proportion with durable complete response, 2.5%, high tox
cytoreductive nephrectomy- should you take primary out?
2 studies with improved survival with this approach: do if no brain mets and safe procedure before starting meds
MSKCC risk groups (prognostic)
KPS<80, short time to need for treatment 12mo, low Hgb, high Ca, high LDH. favorable 0, 1-2 int, 3-5 poor.
temsirolimus FDA approval
used for the poor risk group only
histotypes of RCC
75% clear cell, 15% papillary, 5% chromophobe, 5% oncocytoma, rare others
clear cell RCC
VHL mutation (70-70%), LOH (3p25), or hypermethylation
Type 1 papillary RCC
c-met mutation
Type 2 papillary RCC
FH mutation
VHL gene
tumor supresssor that regulates angiogenesis and cell proliferation. turns off wit hypoxia–>allows HIFa–> (VEGF, PDGF, TGF/EGFR). Mutation is constitutively off
sorafenib for RCC
improved PFS 5.9v 2.8mo compared to placebo, only 2% PR but 78% SD.
sorafenib/nexavar tox
RASH, hand/food in high proportions.
first line RCC
sunitinib (biggest trial), bev+IFN, pazopanib (smaller trial), temsiroliumus (poor risk). no comparatives with each other.
high risk RCC first line
temsirolimus (better than IFN or IFN/tem), IV weekly. more SD, low ORR.
tox, temsirolimus
rash, LE dema, stomatitis, hypergly, HL, thrombocytopenia, dyspnea. (borderline DM tips them over)
sunitinib toxicity
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.
pazopanib tox
less fatigue, hand food, stomatitis, but more liver toxicity
pazopanib v. sunitinib (COMPARZ)
1100pts, NONINFERIOR. sunitinib more fatigue, count suppression. pazopanib has more LFTs, and hair color changes.
pazopanib LFT ab
if prolonged, then switch to sunitinib
everolimus versus placebo in RCC
approved for third line
tox of everolimus
pneumonitis.
axitinib for RCC
most selective for VEGF. improved PFS compared to sorafenib in 2nd line setting.
tox of axitinib
diarrhea, HTN.
when to give everolimus?
either second line or beyond, doesn’t really matter when
nivolumab dosing in RCC
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.
Birt-Hogg-Dube
-ch1, -Y. associated with chromophobe and oncocytoma variation. also has pulmonary nodules/hamartomas.
hereditary papillary RCC
associated with c-met activating mutation, or hydratase inactivating mutation
Stauffer syndrome
paraneoplastic liver failure that reverses with nephrectomy for RCC
VHL syndrome
RCC, retinal angiomas, hemangioblastomas of CNS, pheochromocytomas
VHL genetics
loss of VHL–>loss of ubiquitinization of HIF1a–>increased HIF1a–> increased VEGF/PDGF
medullary carcinoma of kidney
associated with sickle cell
type I papillary RCC
good prognosis
type II papillary RCC
associated with poor prognosis
treatment of RCC with bev
bev+IFN better than IFN alone; monotherapy is not tested
first line RCC, good risk
pazopanib or sunitinib; pazopanib- less fatigue/hand food, thrombocytopenia, mucositis; more LFT abnl
high risk RCC
only temsirolimus approved. 3 or more of the following: LDH, Hgb, Ca,
second line good risk RCC Tx
axitinib OR everolimus. sorafenib worse than axitinib
IL-2 for RCC
can use if good PFS and clear cell variant, in first line
chemotherapy for RCC
if sarcomatoid- gem/dox; if collecting duct- gem/cis; if clear cell- gem/5-FU(or xeloda)
treatment of mTOR-associatead pneumonitis
grade 1- ASx radiographic- monitor and continue; grade 2- Sx mild- hold and give steroids, then dose reduce.
