exam 3 all material

bruh

what is targeted therapy?

A cancer treatment that targets proteins/genes associated with growth and metastasis of cancer

targeted therapy acts on _________

specific molecular targets

targeted therapy is ____ and chemotherapy is ____

a. cytotoxic, cytotoxic

b. cytostatic, cytotoxic

c. cytotoxic, cytostatic

d. cytostatic, cytostatic

b

chemotherapy acts on…

all rapidly dividing cells

why is companion diagnosis essential for targeted therapy? (3)

1. can tell if a pt would benefit from a specific targeted therapy

2. can tell if a pt would be at a higher risk for ADE from specific targeted therapies

3. can monitor treatment and progression in pts on targeted therapy

name the two types of targeted therapy

small molecule inhibitors

monoclonal antibodies

how do small molecule inhibitors work?

they enter cells and inhibit intracellular targets

SMIs:

1. admin route

2. typical targets

1. oral

2. kinases

monoclonal antibodies targets are …

on the cell surface

Which targets intracellular pathways?

a. small molecule inhibitors

b. monoclonal antibodies

a

mabs admin route

IV

common ADE of all targeted therapies (3)

diarrhea, liver problems, and skin problems

other ADE of targeted therapies include… (6)

HTN

Fatigue

Rash

Mouth sores

Nail changes

Loss of hair color

Which oncogene is most commonly mutated?

RAS

What happens when Ras is mutated?

cancer growth due to constant activation

what type of receptor is EGFR?

tyrosine kinase receptors

when EGFR is activated, it leads to…

increased proliferation

increased metastasis

decreased apoptosis

cells expressing EGFR are resistant to…

cytotoxins

Which receptor is important in breast cancer?

HER2

of the HER dimers, which is the most potent and activates RAS MAPK and the STAT pathways?

HER1/HER2

name the antiEGFR mabs

Cetuximab

panitumumab

which drugs targets HER2

Trastuzumab

pertizumab

Trastuzumab MOA

downregulates HER2 signaling by masking protease cleavage site and blocking shedding of the receptor

ultimately leads to activation of the TK domain to

consequences of HER targeted therapies

drug resistance

name 4 tyrosine kinase inhibitors

Afatinib

Erlotinib

getitinib

osimertinib

Afatinib

1. class

2. target

3. fatal ADE

1. SMI / EFGR TKI

2. TK EGFR, HER 2, and HER4

3. interstitial lung disease, sepsis, and pneumonia

Erlotinib

1. target

2. most common ADE

1. TK EGFR

2. rash and diarrhea

name the EGFR TKIs

1. Gefitinib

2. erlotinib

3. afatinib

4. osimertinib

name the multikinase TKIs

Sunitinib

sorafenib

what does ALK code for

tyrosine kinases

MOA of ALK tyrosine kinase inhibitors

competitive inhibition of the ATP binding site on the ALK receptor

name the ALK TKIs

crizotinib

ceritinib

alectinib

lorlatinib

ceritinib targets (4)

tyrosine kinase, ALK, IGF1, and ROS1

Alectinib targets

ALK and RET

Lorlatinib and brigatinib targets

ALK and ROS1

what proteins are considered molecular switches?

RAS

Dabrafenib

1. class

2. target

3. severe ADE

1. SMI

2. BRAF

3. carcinoma, hypotension, kidney failure

name the MEK inhibitor

Trametinib

Trametinib

1. class

2. target

3. ADE

1. SMI

2. MEK

3. rash, diarrhea, edema

name the CDK inhibitor

Palbociclib

name the PI3K inhibitor

Idelalisib

name the mTOR inhibitor

Everolimus

what pathway promotes growth / proliferation

RAS / MAPK

what pathway promotes survival (anti-apoptosis)

PI3K / AKT / mTOR

which pathway promotes the cell cycle division

CDK

name the proteins that are pro-apoptosis

BAD

NOXA

BAX

BAK

name the proteins that are anti-apoptosis

Bcl-2

Bcl-xl

Which of the following does not promotes apoptosis?

a. bcl-2

b. NOXA

c. BAD

d. BAK

a

what is nausea

feeling like you are going to throw up / queasy feeling

what is vomitting?

expelling the contents of the GIT

what are the 4 types of N/V associated with chemo?

1. anticipatory

2. acute

3. delayed

4. breakthrough

define anticipatory CINV

N/V before chemotherapy likely due to anxiety from a previous bad reaction

define acute CINV

occurs on day 1 of chemo

define delayed CINV

occurs after day 1 of chemotherapy to day 5 of chemo

define breakthrough CINV

N/V that can occur at any time during chemotherapy

what are some risk factors of acute CINV

women, younger age, chemotherapy regimen

name the 4 medications/ classes that are indicated for acute CINV prophylaxis

5HT3 inhibitors (-setron)

NK1 antagonists (-pitant)

dexamethasone

olanzapine

name the 3 medications/ classes that are indicated for delayed CINV prophylaxis

NK1 antagonists (-pitants)

dexamethasone

olanzapine

which of the following drugs/classes is NOT indicated for delayed CINV prophylaxis?

a. olanzapine

b. dexamethasone

c. NK1 antagonists

d. 5HT3 inhibitors

d

NK1 antagonist medications all end with…

-pitant

which class of medications has long half lives so the effects last for multiple days?

NK1 antagonists

T or F:

NK1 antagonists are generally well tolerated

T

NK1 antagonists are ____ therapy only

a. mono

b. combo

b

when would NK1 antagonists be given for CINV prophylaxis and why?

day 1 of chemotherapy because they treat acute N/V and last for a long time

5HT3 antagonists all end with…

-setron

-setron is the suffix for which class of medications?

5HT3 inhibitors

which class of agents for CINV is associated with QTc prolongation?

-setrons (5HT3 inhibitors)

-setrons (5HT3 inhibitors) are associated with causing what severe ADE?

QTc prolongation

what patient demographics are at higher risk of QTc prolongation while on 5HT3 inhibitors?

CHF

congenital QTc prolonging syndrome

bradyarrhythmias

taking other meds that can prolong QTc

most important patient counseling for 5HT3 inhibitors

keep track of other QTc prolonging agents

counseling points for 5HT3 inhibitors (-setrons)

keep track of other QTc prolonging agents

maintain K and Mg levels

what is the maximum dose of ondansetron? and the method of delivery?

16 mg IV

which delivery method of 5HT3 inhibitors (-setrons) is known to cause more QTc prolongation?

IV

which 5HT3 inhibitors (-setron) has the lowest risk of QTc prolongation?

palonosetron

5HT3 inhibitors (-setron) ADEs

QTc prolongation

HA

constipation

high emetic risk prophylaxis:

day 1 regimen (aka acute tx)

NK1 antagonist (-pitant)

5HT3 inhibitor (-setron)

Dexamethasone

Olanzapine

high emetic risk prophylaxis:

days 2-4 regimen

Dexamethasone 8 mg PO or IV daily

Olanzapine 2.5-10 mg PO qhs

olanzapine main ADE

sedation

moderate emetic risk acute CINV prophylaxis:

pt on high dose carboplatin regimen

NK1 antagonist (-pitant)

5HT3 inhibitor: (-setron)

Dexamethasone 12 mg PO or IV

moderate emetic risk acute CINV prophylaxis:

pt on low dose carboplatin or not on carboplatin regimen

5HT3 inhibitor (-setron)

Dexamethasone 8 mg PO or IV

Moderate emetic risk for delayed CINV prophylaxis:

these pts only need to be treated if they are on…

agents with increased risk of N/V

Moderate emetic risk for delayed CINV prophylaxis:

treatment (must be on agent with increased risk)

dexamethasone

low emetic risk acute CINV prophylaxis:

OPTIONS

dexamethason 8 mg PO or IV

OR
5HT3 inhibitor (-setron)

low emetic risk delayed CINV prophylaxis:

regimen

none, tricked you 🤪

how to prevent anticipatory CINV?

use appropriate anti-emetic prophylaxis so they dont get anxiety about it

most effective method of anticipatory CINV treatment

behavioral therapy

anticipatory CINV:

tx options

po benzo the night before treatment and 1-2 hrs before chemotherapy

or

olanzapine 2.5-5 mg the night before chemotherapy

anticipatory CINV:

what benzo and dose is typically used?

lorazepam 0.5-1 mg

breakthrough emesis:

how to treat?

add another agent with a different MOA

if the med is working switch from prn to scheduled dosing

ORAL chemo CINV moderate to high risk prophylaxis:

treatment options

5HT3 inhibitor PO 30 min b4 medication

or

olanzapine 2.5-10 mg PO qhs

ORAL chemo CINV low to minimal risk prophylaxis:

treatment options

nothing or have a breakthrough medication ready (tbh im confused)

name the three kinds of bone marrow suppression that can be caused by malignancy or cancer treatment

anemia

thrombocytopenic

neutropenia

neutropenia is defined as an ANC of ____

<500

neutropenia puts pts at increased risk of _____

infections

what is the formula for ANC?

(% segs + % bands) x WBC

febrile neutropenia definition

have a temp of >/= 101 once or >/= 100.4 sustained

and ANC < 500

febrile neutropenia can lead to alterations in which barriers of the body?

skin, GIT, lungs

most common organisms that cause febrile neutropenia include…

bacteria, fungus, and viruses

what type of bacteria is mostly associated with causing febrile neutropenia

gram negative

which gram negative bacteria is the most likely cause of febrile neutropenia?

pseudomonas