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PHM 703: Crit Care/Heme/Onc > Onco 2: Lung and Kung pao chicken > Flashcards

Onco 2: Lung and Kung pao chicken Flashcards

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1
Q

lung cancer patho

A
  • 1: acquire molecular lesions (smoking, DNA)
  • 2: one or more of the folowing
    - inhition of tumor suppessor genes
    - production of autocrine growth factors
    - immune system evasion
    - activation of proto-oncogenes
  • 3: increased cell division
  • 4: tumor
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2
Q

lung cancer types

A
  • small cell lung cancer
  • nonsmall cell lung cancer
    - squamous
    - non-squamous: large cell and adenocarcinoma
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3
Q

NSCLC staging

A
  • stage 2: confied to lung
  • stage 2: ipsilateral lymph node involvement
  • stage 3: more extensive node involvement
  • stage 4: distant metastases

stage 4 - prolong survival

treatment intent stage 1-3 - cure

early stage: stage 1-2, N0
locally advanced: stage 2-3 N(+)
advanced/metastataic: stage 4

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4
Q

SCLC vs NSCLC

A

small cell:
- more aggressive
- faster growth
- worse prognosis
- surgery treatment is rare
- canNOT use targeted therapy

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5
Q

SCLC staging

A
  • limited stage: confied to one lung +/- lypmh node involvement on same side
  • extensive stage: both lungs+/- lypmh node nvolvement on both sides; extrapulmonary metastases

cure for limited, prolong survivail for extensive

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6
Q

presentation of lung cacner

A
  • pulmonary: cough, dyspnea, chest pain
  • extra-pulmonary: fatigue, wt loss, anorexia
  • superior vena cava syndroem: swellign in face and neck dt tumor blocking/pressing against SVC
  • CNS metastates -> neuro s/s
  • paraneoplastic synndroems (more common in SCLC than NSCLC): hyper Ca, SIADH

red flags: repeat rx for PNA, bronchitis, chronic cough

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7
Q

risk factors for lung cancer

A
  • smoking (and expsoure to smoke)
  • asbestos
  • metal (arsenic) exposure
  • radiation
  • air pollution
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8
Q

pack eyars

A
  • measure of lifetime smoking hx
  • = years smoked x PPD

1 pack = 20cigs

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9
Q

lung cancer screening

A
  • yearly low dose CT scan
  • only screen hgiih risk pts - defined by UPSTF to have all(?) of the following
    - age 50-80
    - 20 pack year smoking hx
    - current smoker OR former who quit in past 15 yrs
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10
Q

why don’t we bother screening everyone for lung cacner

A
  • false (+) -> uncessary treatment
  • cost
  • radiation exposure
  • some pts may not even be able to tolerage chemo
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11
Q

diagnosing lung cacner

A
  1. radiologic eval (CT)
  2. lung tissue biopsy: confirms presence and determines tumor type
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12
Q

NSCLC treatment: stage 1

A
  • surgical resection
  • if unresectable -> radiation
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13
Q

perioperative aduvant therapy

definition

A

before or after or both (includes neo/new and adjuvant/after)

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14
Q

neoadjuvant optiosn for NSCLC

A
  • nivolumab + platinum for 3 cycles
  • pembrolizumab + cisplatin 4 cycles
  • if NOT a candidate for immune checkpoint inhibitor: platinum 4 cycles

if pembrolizumab is used for neoadjuvant, use it for adjuvant

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15
Q

adjuvant options for NSCLC

post surgery

A
  • if EGFR (+): osimertinib QD up to 3 yrs
  • atezolizumab up to 1 yr
  • pembrolizumb 1 yr
  • if not a candidate for immune checkpoint inhibitor: platinum 4 cycles
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16
Q

NSCLC treatment: stage 2

A
  • resectable: surgery + adjuvant chemo (consider neoadjuvant)
  • unresectable: chemo + radiation
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17
Q

NSCLC treatment: stage 3

A
  • resectable: neadjuvant + surgery + adjuvant (+/- radiation)
  • unresectable: chemo + radiation + durvalumab maintenace

neoadjuvant chemo: shrinks tumor, amkes surgery easier

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18
Q

platium therapy options in NSCLC

A
  • non-squamous: cisplatin/pemtrexed
  • squamous: cisplatin + (docetaxel or gemcitabine)
  • if pt unable to use/tolerate cisplatin: carboplatin + (paclitaxel or gemcitabine or pemetrexed)
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19
Q

pemetrexed can only treat _____

A

nonsquamous

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20
Q

ciplatin vs carboplatin

A
  • cisplatin just a teensy bit better for treating (but more or less comparable efficacy)
  • cisplatin more ADR:
    - N/V
    - nephrotox (hypoMg and K)
    - ototox
    - peripheral neuroapthy
  • carboplatin: more thromocytopenia and dose takes into acount renal fxn
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21
Q

calculating carboplatin dose

A
  • determine wt
    - IBW = (50 or 45.5) + 2.3(inches - 60)
    - if ABW = 1.2 x IBW, use adj BW (=IBW + 0.4 (ABW-IBW)
    - if ABW < IBW: use ABW
  • CrCl (Cockcoft Grault) - Meaney would be big sad if you didn’t already have this memorized
  • Calvert equation: total mg = (total AUC)(CrCl + 25)

CrCl canNOT exceed 125

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22
Q

NSCLC stage I-3 chemo classes/options/agents

A
  • Taxanes: paclitaxel, docetaxel
  • Pemetrexed

platinum base

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23
Q

taxanes MOA

A

disrupt microtubule depolyermiaztion -> inhibit mitosis

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24
Q

taxanes DDI

A
  • CYP3A4
  • paclitaxel also has 2C8
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25
taxanes ADR
- alopecia - like loss of all hair - peripheral neuropahty - solven related hypersensitivy -> premedicat with beandryl, famotidine, dexamethasone - docetaxel: peripehral edema -> premedicate with dexamethasone on day before, of and after
26
pemetrexed MOA
inhibit DHFR (folate) and TS -> deplete purine and pyrimidine sythesis (DNA building blocks) | requires B12 and folic acid supplement
27
pemetrexed admin/dose considerations
- renally elimated: increased tox in CrCl < 45 -> avoid - NSAIDs reduce clearance -> avoid
28
pemetrexed ADDR
erythematous/pruitic rash -> premedicate wth dexamethasone on day before, of and after
29
NSCLC stage 4/relapsed treatment
- targetable mutations -> use kinase inhibitor that targets that mutation - if no targetable mutations: look at PD-L1 status - PD-L1 >1: PD-1/PD-L1 +/- chemo (def give chemo if 1-49%) - PD-L1 < 1: PD-1/PD-L1 WITH chemo
30
targetable NSCLC mutations | only use targeted treatment in stage 4
- EGFR: mutation at exon 18-24 - drugs target 19 and 21 (20 is super bad btw) - more common in nonsmokers - ALK - KRAS: KRAS targeted therapy only indicate din advanced/metastattic NSCLC and KRAS G12C mutation *afer 1 prior therapy* - more common in smokers, bad pronosis factor | all these are PO agents
31
EGFR inibitor TKI agents
- 1st gen: erlotinib, Gefitinib afatinib - 2nd gen: dacomitinib (preferred over 1st gen dt better outcomes) - 3rd gen: osimertinib: first line dt better outcomes, tolerability, and CNS penetration | CNS penetration kind of wanted dt risk of CNS metastases
32
EGFR inhibitor TKI DDI
- all have CYP 3A4 (except dacomitinib) - CYP 2D6: dacomitinib and gefitinib
33
EGFR TKI general ADR
- dry skin - nail fragility - conjuntivitis - diarrhea - acneiform rash
34
osimertinib specfic ADR
- myelosuppression - QT prolongation - stomatitis - fatigue
35
how to treat/handle an acneiform rash
- grade 1: mild - topical steroid or topical ABX - grade 2: mod - topical steroid and PO ABX - grade 3: severe - delay chemo 1-2 W; above treatments + PO steroid | for grade 3, MAY dose reduce CHEMO once restarting ## Footnote - avoid OTC acne products, dryign
36
ALK inhibitor agents
- 1st gen: crizotinib, certinib - 2nd gen: alectinib, brigatinib - 3rd gen: loralatinib - has better CNS potency and BBB penetration | 2nd and 3rd gen preferred for better outcomes
37
ALK inhibitor DDI
- all have CYP 3A4 - lorlatinib also has Pgp
38
ALK inhibitor class/general ADR
- all gen: fatigue - 2nd and 3rd gen: myalgias
39
brigatinib specific ADR | 2nd gen ALK inhibitor
- pneumonitis - HTN
40
alectinib specific ADR | 2nd gen ALK inhibitor
- LFTs, hepatotox - anemia - peripheral edema | A=anemia L=LFT,liver E= edema, peripheral
41
lorlatinib specific ADR | 3rd gen ALK inhibitor
- peripheral edema, weight - neuro - HLD - arthralgia
42
KRAS inhibitor agents
- sotorasib - adagrasib
43
sotorasib admin/dose considerations
- 8T QD but can be reducd based on ADR - avoid H2RA and PPI 4hr before adn 10 hr after
44
sotorasib ADR | KRAS
- nausea, diarrhea - fatigue - anemias - muscle pain
45
sotorasib DDI
CYP3A4 and Pgp
46
adagrasib admin
3T BID - can dose reduce if ADR | does NOT have the same issues with PPIs and H2RAs as storasib
47
adagrasib DDI
- CYP3A4 - inhibits own metabolism at ss - moderate: CYP2B6, 2C9, Pgp
48
adagrasib ADR | KRAS
same as sotorasib: - nausea, diarrhea - fatigue - anemias - muscle pain ## Footnote also - renal impairment - edema - QT prolongation - pneumonitis
49
immunotherapy single agents (PD-1/PD-L1)
- pembrolizumab - atezolizumab - cemiplimab
50
immunotherapy (PD-1/PD-L1) + chemo combos
- squamous: carboplatin + paclitaxel + pembrolizumab - non-squamous: - (cisplatin OR carboplatin) + pemetrexed + (pembrolizumab or cemiplimab) - (cisplatin OR carboplatin) + paclitaxel + cemiplimab
51
NSCLC progression / second line therapy in pts who previously received immune therapy
give chemo - docetaxel + ramucirumab (preferred) - docetaxel - gemcitaine - albumin-bound paclitaxel - pemetrexed (nonsquamous)
52
NSCLC progression / second line therapy in pts who previously did NOT received immune therapy
give immunotherapy - pembrolizumab - nivolumab - atezolizumab
53
immunotherapy ADR
inflammation - v bad - avoid in pts with pre-existing autoimmune disease - onset can be anytime (though earlier onset, increased incidence, worse ADR if pt receiving PD/CTLA-4 ## Footnote - immune-mediated reactions - colitis - rash - hepatiitis - nephritis - pneumonitis - thyroid disorder
54
management of immunotherapy induced inflammation
- grade 1: continue therapy - grade 2: hold and consider CS - grade 3: hold and def give CS - refractory ## Footnote CS: prednisone 0.5-2mg/kg/day until resolution to grade 1 (or equivalent)
55
NSCLC adjunctive therapy
VEGF inhibitors | NSCLC agents: Bevacizumab, Ramucirumab
56
VEGF inhibitor agents for adjuvant use in NSCLC
- bevacizumab - avoid in squamous (bleed) - ramucizumab
57
VEGF inhibitor ADR
- acute: HTN (**unontrollled HTN is a CI for bevacizumab**) - chronic - thromboembolic - epistaxis (nosebleed) - delayed wound healing -> dc bevacizumab 4 wk before and after surgery - perforation - proteinuria - dish soap irine - diarrhea (ramucizumab) ## Footnote avoid in recent hemoptysis, tpx anticoag, new onset VTE, recent surgery
58
SCLC tretament
chemo +/- radiation **limited stage:** * (carbo or cisplatin) + etoposide + radiation **extensive** - carboplatin + etoposide + (atezolizumab or durvalumab) - cisplatin + etoposide + durvalumab
59
when is carboplatin preferred over cisplatin in lung cancer
SCLC extensive - pts too poor to really tolerate cisplatin
60
Etoposide ADR
myelosuppression
61
Etoposide MOA
dsDNA breaks | topo 2 inhibitor
62
2nd line therapy for SCLC
- topotecan PO or IV - renal dose adjust - lurbinectedin - clincal trial | lurb: check liver, nausea, give dex
63
Topotecan ADR
- myelosuppression - neutropenia
64
Topotecan MOA
ssDNA breaks | topo 1 inhibitor
65
Luribinectedin ADR
- fatigue - nausea - LFTs -> pretreat with dexxamethasone adn 5-HT3 - extravasation

PHM 703: Crit Care/Heme/Onc (16 decks)

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