Lecture 6 Flashcards
Lung cancer
What are the leading risk factors of lung cancer ?
Smoking ( 1st and 2nd), Asbestos, COP, TB, lupus, immunosuppressive, exposure to radiation, pollution , beta carotene with smoking, certian chemicals exposure
Cannabis ? e-cigarette?
How often should people be screened ?
low dose of CT scane every 3 years in those ….
Who should be screened
55-74 years
15 yearsof smoking
30 pack per year
What are the S/S of Lung cancer?
cough, dyspnea, weight loss, chest pain and looks similar to COPD
Which type of lung cancer is most common among non-smokers ?
NSCLC - adenocarcinoma “gland”
What is the difference between mAb and small molecules ?
mAb mostlywork outside
small molecules - intracellular , not protein bound, short 1/2 lives and frequent dosing
What are the predictive biomarkers for NSCLC ?m
EGFR mutation
ALK rearrangement
ROS1 mutation
BR mutation
PDL-1+ ( >50%)
Predictive biomarker Negative
On the T cells what are the brakes and the gas pedals receptors ?
CTLA4 and PD1 –> Brakes , don’t kill
CD28 and OX40 –> kill
what is TPS in NSCLC?
Tmour proportion score
% of viable tumour celss showing PDL-1
What is Tx options for NSCLC stage 2 resectable ?
SurgerySurgery Resection
/ - Adjuvant
/- Adjuvant radiation or re-resection
Or EGFR + → osimertinib
What is the Tx options if stage 3 non - resectable ?
Radiation + chemo
Neoadjuvant
Adjuvant (chemo or radiation)
~ surgery ?!
Stage 3a - good response: durvalumab maintenance
What is the technique for NSCLC adjuvant tx?
Platinum doublet ( platinum + another)
Carboplatin or cisplatin
Vinorelbine or Gemcitabine
Tx for EGFR mutation ?
Osimertinib
Tx for PDL1 > 50% mutation ?
Atezolizumab/ Durvalumab
( stops the brake)
Tx for PD1 mutation ?
Nivolumab or pembrolizumab
(stops the break)
Tx for CTLA mutation ?
Ipilimumab
Stops the break
Why is carboplatin is prefered over cisplatin ?
less SE ( nausea, ototoxicity, nephrotoxicity)
More myelosuppression ( less WBCs risk)
Which medication would you use Calvert equation ?
Caboplatin
What is the MOA of vinorelbine ?
Vinca alkaloid
Inhibits cell growth by binding to tubulin on mitotic
what are the side effects of virorelbine ?
Myelosuppression
Changes to bowel ( constipation or diarrhea)
neuropathy
alopecia
bine –> bowel
What are the SE of gemcitabine ?
Bonne marrow suppression
Elevated liver function
pulmonary toxicity
When would you use pemetrexed ?
in the second agent for platinum doublet in PALLIATIVE care
What are the SE of premethexed ?
Bone marrow suppression
Diarrhea
Mucositis
Fatigue
Rash ( solution CS)
What is a side effect prevention with premetrexed ?
Folic acid
Vitamin B12
When would you use precision medicine ?
advanced or metastases
evidence of gene mutations
Why is osimertinib so preferred and when should it be used ?
Used as the preferred EGFR TKI –> activity against resistance , better penetrance across BBB
ONLY indicated adjuvant and preferred metastatic
For how long can you have osimertinib for adjuvant setting ?
up to 3 years
Name EGFR TKi for lung cancer and when it would be used ?
Erlotinib
Gefitinib
Afatinib
Osimertinib *** ( can be in adjuvant)
mostly in advanced staged NSLCL
If a patient comes in to pick up osimertinib ? what counselling point can you give ?
2 weeks can get rash like acne with papules and red , worse with sun
Diarrhea ( loperamide)
Fatigue
What f/u and monitoring should you do for EGFR TKi medications - lung cancer ?
LFTs
QTc
Rash
Diarrhea
Other drugs like CYP3A4 : rifampin, anticonvulsants, macrolides
Why might we want to use medications for ROS1 ?
it is a TK that plays a role in signalling of the cells .
Also a proto-ocogene
What are the SE of Crizotinib vs Entrectinib ?
Crizo ( eye problem)
Entre ( Cognitive and CNS)
What are the SE of Brigatinib?
More risk of highmBG, HTN, High CK
What are the various TKI ( ROS1, ALK,EGFR) DDI ?
CYP 3A4
PH dependent
QT prolongation
Which of the TKI ( ALK, ROS1, EGFR) needs a high fat meals for absorption ?
Alectinib
What should a pt avoid while on TKI for lung cancer ?
3A4 - grapefruit
pH = PPI, H2 antagonist
What are PDL1i ?
Atezolimuab and Durvalumab
What are PD1i ?
Nivolumab and prembrolizumab
Name PDL1i ?
PEDAL
Durvalumab
Atezolimuab
What does PDL1 TPS > 50% ?
high expression of PD L1 on the tumour cells and pt would benefit from mAb Tx
Looking at immune checkpoint Tx , pt has stage 2 lung cancer , PD>50% ?
recommended tx
Atezolizumab
Looking at immune checkpoint Tx , pt has stage 3c lung cancer , PD>50% ?
recommended tx
Durvalumab
Pt with Met-NSCLC with no driver mutations , what are the different tx ?
Platinum Doublet
ICI mono ( pembrolizumab)
Platinum doublet + ICI tx ( one or two)
What does the research say about the use of CTL4i and PD1i ?
No clinical evidence now but is founded by the government
If a patient has a low ECOG , which Tx would you recommend ?
Low chemo/radiation dose
when is it appropriate to give durvalumab in NSLCL ?
curative - stage 3A
maintenance therapy ( after chemo+ radiation that had a good response)
What is the main difference between SCLC limited vs extensive ?
Limited : in one area that can be treated with radiotherapy
Extensive: spread to nodes
Palliative pts
What are the main point of SCLC ?
Highly linked to smoking
Grows fast and spreads easily
people get sick faster and reach stage 4
What is the common metastase of lung cancer ?
brain
What is the prime indication for etoposide ?
SCLC ( small cells lung cancer)
If a patient has a good response to chemo and radiotherapy , what is the next step ?
SCLC limited .
prophylactic brain radiation
SCLC spread fast and grows fast
What are the tx for extensive SCLC ?
Platinum doublet ( with etoposide)
PDL1
What are the SE of etoposide ?
Hypotension while infusion
mucositis/ stomatitiss
Alopecia
Bone marrow suppression
Allergic / hypersensitivity rxn
What is the MOA of etoposide ?
topoisomerase II inhibitor
What is the oral bioavailibility of etoposide ?
Oral is approximately 50% bioavailable so dose of oral is usually increased
by a factor of 2 as compared to IV
