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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

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
Q

taxanes ADR

A
  • 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
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26
Q

pemetrexed MOA

A

inhibit DHFR (folate) and TS -> deplete purine and pyrimidine sythesis (DNA building blocks)

requires B12 and folic acid supplement

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27
Q

pemetrexed admin/dose considerations

A
  • renally elimated: increased tox in CrCl < 45 -> avoid
  • NSAIDs reduce clearance -> avoid
28
Q

pemetrexed ADDR

A

erythematous/pruitic rash -> premedicate wth dexamethasone on day before, of and after

29
Q

NSCLC stage 4/relapsed treatment

A
  • 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
Q

targetable NSCLC mutations

only use targeted treatment in stage 4

A
  • 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
Q

EGFR inibitor TKI agents

A
  • 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
Q

EGFR inhibitor TKI DDI

A
  • all have CYP 3A4 (except dacomitinib)
  • CYP 2D6: dacomitinib and gefitinib
33
Q

EGFR TKI general ADR

A
  • dry skin
  • nail fragility
  • conjuntivitis
  • diarrhea
  • acneiform rash
34
Q

osimertinib specfic ADR

A
  • myelosuppression
  • QT prolongation
  • stomatitis
  • fatigue
35
Q

how to treat/handle an acneiform rash

A
  • 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

  • avoid OTC acne products, dryign
36
Q

ALK inhibitor agents

A
  • 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
Q

ALK inhibitor DDI

A
  • all have CYP 3A4
  • lorlatinib also has Pgp
38
Q

ALK inhibitor class/general ADR

A
  • all gen: fatigue
  • 2nd and 3rd gen: myalgias
39
Q

brigatinib specific ADR

2nd gen ALK inhibitor

A
  • pneumonitis
  • HTN
40
Q

alectinib specific ADR

2nd gen ALK inhibitor

A
  • LFTs, hepatotox
  • anemia
  • peripheral edema

A=anemia
L=LFT,liver
E= edema, peripheral

41
Q

lorlatinib specific ADR

3rd gen ALK inhibitor

A
  • peripheral edema, weight
  • neuro
  • HLD
  • arthralgia
42
Q

KRAS inhibitor agents

A
  • sotorasib
  • adagrasib
43
Q

sotorasib admin/dose considerations

A
  • 8T QD but can be reducd based on ADR
  • avoid H2RA and PPI 4hr before adn 10 hr after
44
Q

sotorasib ADR

KRAS

A
  • nausea, diarrhea
  • fatigue
  • anemias
  • muscle pain
45
Q

sotorasib DDI

A

CYP3A4 and Pgp

46
Q

adagrasib admin

A

3T BID - can dose reduce if ADR

does NOT have the same issues with PPIs and H2RAs as storasib

47
Q

adagrasib DDI

A
  • CYP3A4 - inhibits own metabolism at ss
  • moderate: CYP2B6, 2C9, Pgp
48
Q

adagrasib ADR

KRAS

A

same as sotorasib:
- nausea, diarrhea
- fatigue
- anemias
- muscle pain

also
- renal impairment
- edema
- QT prolongation
- pneumonitis

49
Q

immunotherapy single agents (PD-1/PD-L1)

A
  • pembrolizumab
  • atezolizumab
  • cemiplimab
50
Q

immunotherapy (PD-1/PD-L1) + chemo combos

A
  • squamous: carboplatin + paclitaxel + pembrolizumab
  • non-squamous:
    - (cisplatin OR carboplatin) + pemetrexed + (pembrolizumab or cemiplimab)
    - (cisplatin OR carboplatin) + paclitaxel + cemiplimab
51
Q

NSCLC progression / second line therapy in pts who previously received immune therapy

A

give chemo
- docetaxel + ramucirumab (preferred)
- docetaxel
- gemcitaine
- albumin-bound paclitaxel
- pemetrexed (nonsquamous)

52
Q

NSCLC progression / second line therapy in pts who previously did NOT received immune therapy

A

give immunotherapy
- pembrolizumab
- nivolumab
- atezolizumab

53
Q

immunotherapy ADR

A

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

  • immune-mediated reactions
    • colitis
    • rash
    • hepatiitis
    • nephritis
    • pneumonitis
    • thyroid disorder
54
Q

management of immunotherapy induced inflammation

A
  • grade 1: continue therapy
  • grade 2: hold and consider CS
  • grade 3: hold and def give CS
  • refractory

CS: prednisone 0.5-2mg/kg/day until resolution to grade 1 (or equivalent)

55
Q

NSCLC adjunctive therapy

A

VEGF inhibitors

NSCLC agents: Bevacizumab, Ramucirumab

56
Q

VEGF inhibitor agents for adjuvant use in NSCLC

A
  • bevacizumab - avoid in squamous (bleed)
  • ramucizumab
57
Q

VEGF inhibitor ADR

A
  • 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)

avoid in recent hemoptysis, tpx anticoag, new onset VTE, recent surgery

58
Q

SCLC tretament

A

chemo +/- radiation
limited stage:
* (carbo or cisplatin) + etoposide + radiation

extensive
- carboplatin + etoposide + (atezolizumab or durvalumab)
- cisplatin + etoposide + durvalumab

59
Q

when is carboplatin preferred over cisplatin in lung cancer

A

SCLC extensive - pts too poor to really tolerate cisplatin

60
Q

Etoposide ADR

A

myelosuppression

61
Q

Etoposide MOA

A

dsDNA breaks

topo 2 inhibitor

62
Q

2nd line therapy for SCLC

A
  • topotecan PO or IV - renal dose adjust
  • lurbinectedin
  • clincal trial

lurb: check liver, nausea, give dex

63
Q

Topotecan ADR

A
  • myelosuppression
  • neutropenia
64
Q

Topotecan MOA

A

ssDNA breaks

topo 1 inhibitor

65
Q

Luribinectedin ADR

A
  • fatigue
  • nausea
  • LFTs -> pretreat with dexxamethasone adn 5-HT3
  • extravasation

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

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