Onco 2: Lung and Kung pao chicken Flashcards
lung cancer patho
- 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
lung cancer types
- small cell lung cancer
- nonsmall cell lung cancer
- squamous
- non-squamous: large cell and adenocarcinoma
NSCLC staging
- 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
SCLC vs NSCLC
small cell:
- more aggressive
- faster growth
- worse prognosis
- surgery treatment is rare
- canNOT use targeted therapy
SCLC staging
- 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
presentation of lung cacner
- 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
risk factors for lung cancer
- smoking (and expsoure to smoke)
- asbestos
- metal (arsenic) exposure
- radiation
- air pollution
pack eyars
- measure of lifetime smoking hx
- = years smoked x PPD
1 pack = 20cigs
lung cancer screening
- 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
why don’t we bother screening everyone for lung cacner
- false (+) -> uncessary treatment
- cost
- radiation exposure
- some pts may not even be able to tolerage chemo
diagnosing lung cacner
- radiologic eval (CT)
- lung tissue biopsy: confirms presence and determines tumor type
NSCLC treatment: stage 1
- surgical resection
- if unresectable -> radiation
perioperative aduvant therapy
definition
before or after or both (includes neo/new and adjuvant/after)
neoadjuvant optiosn for NSCLC
- 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
adjuvant options for NSCLC
post surgery
- 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
NSCLC treatment: stage 2
- resectable: surgery + adjuvant chemo (consider neoadjuvant)
- unresectable: chemo + radiation
NSCLC treatment: stage 3
- resectable: neadjuvant + surgery + adjuvant (+/- radiation)
- unresectable: chemo + radiation + durvalumab maintenace
neoadjuvant chemo: shrinks tumor, amkes surgery easier
platium therapy options in NSCLC
- non-squamous: cisplatin/pemtrexed
- squamous: cisplatin + (docetaxel or gemcitabine)
- if pt unable to use/tolerate cisplatin: carboplatin + (paclitaxel or gemcitabine or pemetrexed)
pemetrexed can only treat _____
nonsquamous
ciplatin vs carboplatin
- 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
calculating carboplatin dose
- 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
NSCLC stage I-3 chemo classes/options/agents
- Taxanes: paclitaxel, docetaxel
- Pemetrexed
platinum base
taxanes MOA
disrupt microtubule depolyermiaztion -> inhibit mitosis
taxanes DDI
- CYP3A4
- paclitaxel also has 2C8
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
pemetrexed MOA
inhibit DHFR (folate) and TS -> deplete purine and pyrimidine sythesis (DNA building blocks)
requires B12 and folic acid supplement
pemetrexed admin/dose considerations
- renally elimated: increased tox in CrCl < 45 -> avoid
- NSAIDs reduce clearance -> avoid
pemetrexed ADDR
erythematous/pruitic rash -> premedicate wth dexamethasone on day before, of and after
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
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
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
EGFR inhibitor TKI DDI
- all have CYP 3A4 (except dacomitinib)
- CYP 2D6: dacomitinib and gefitinib
EGFR TKI general ADR
- dry skin
- nail fragility
- conjuntivitis
- diarrhea
- acneiform rash
osimertinib specfic ADR
- myelosuppression
- QT prolongation
- stomatitis
- fatigue
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
- avoid OTC acne products, dryign
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
ALK inhibitor DDI
- all have CYP 3A4
- lorlatinib also has Pgp
ALK inhibitor class/general ADR
- all gen: fatigue
- 2nd and 3rd gen: myalgias
brigatinib specific ADR
2nd gen ALK inhibitor
- pneumonitis
- HTN
alectinib specific ADR
2nd gen ALK inhibitor
- LFTs, hepatotox
- anemia
- peripheral edema
A=anemia
L=LFT,liver
E= edema, peripheral
lorlatinib specific ADR
3rd gen ALK inhibitor
- peripheral edema, weight
- neuro
- HLD
- arthralgia
KRAS inhibitor agents
- sotorasib
- adagrasib
sotorasib admin/dose considerations
- 8T QD but can be reducd based on ADR
- avoid H2RA and PPI 4hr before adn 10 hr after
sotorasib ADR
KRAS
- nausea, diarrhea
- fatigue
- anemias
- muscle pain
sotorasib DDI
CYP3A4 and Pgp
adagrasib admin
3T BID - can dose reduce if ADR
does NOT have the same issues with PPIs and H2RAs as storasib
adagrasib DDI
- CYP3A4 - inhibits own metabolism at ss
- moderate: CYP2B6, 2C9, Pgp
adagrasib ADR
KRAS
same as sotorasib:
- nausea, diarrhea
- fatigue
- anemias
- muscle pain
also
- renal impairment
- edema
- QT prolongation
- pneumonitis
immunotherapy single agents (PD-1/PD-L1)
- pembrolizumab
- atezolizumab
- cemiplimab
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
NSCLC progression / second line therapy in pts who previously received immune therapy
give chemo
- docetaxel + ramucirumab (preferred)
- docetaxel
- gemcitaine
- albumin-bound paclitaxel
- pemetrexed (nonsquamous)
NSCLC progression / second line therapy in pts who previously did NOT received immune therapy
give immunotherapy
- pembrolizumab
- nivolumab
- atezolizumab
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
- immune-mediated reactions
- colitis
- rash
- hepatiitis
- nephritis
- pneumonitis
- thyroid disorder
management of immunotherapy induced inflammation
- 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)
NSCLC adjunctive therapy
VEGF inhibitors
NSCLC agents: Bevacizumab, Ramucirumab
VEGF inhibitor agents for adjuvant use in NSCLC
- bevacizumab - avoid in squamous (bleed)
- ramucizumab
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)
avoid in recent hemoptysis, tpx anticoag, new onset VTE, recent surgery
SCLC tretament
chemo +/- radiation
limited stage:
* (carbo or cisplatin) + etoposide + radiation
extensive
- carboplatin + etoposide + (atezolizumab or durvalumab)
- cisplatin + etoposide + durvalumab
when is carboplatin preferred over cisplatin in lung cancer
SCLC extensive - pts too poor to really tolerate cisplatin
Etoposide ADR
myelosuppression
Etoposide MOA
dsDNA breaks
topo 2 inhibitor
2nd line therapy for SCLC
- topotecan PO or IV - renal dose adjust
- lurbinectedin
- clincal trial
lurb: check liver, nausea, give dex
Topotecan ADR
- myelosuppression
- neutropenia
Topotecan MOA
ssDNA breaks
topo 1 inhibitor
Luribinectedin ADR
- fatigue
- nausea
- LFTs -> pretreat with dexxamethasone adn 5-HT3
- extravasation
