Cardiotoxicity + Thrombosis

Question 1

What cardiotoxicity do Anthracyclines (Cytotoxic antineoplastics) cause

Answer 1

• Acute cardiomyopathy
• Chronic heart failure years later (irreversible)

Question 2

MOA of anthracyclines cardiotoxicity (2)

Answer 2

Thought to be due to:
I. Forms free radicals
II. Destroys cardiomyocytes & mitochondria

Risk increases with greater exposure
* Which is why we limit max dose of doxorubicin

Question 3

How do we manage cardiotoxicity with anthracyclines

Answer 3

Baseline ECG for everyone before starting

1. D/C anthracyclines
2. Treat as acute cardiac failure
   (diuretics, ACE/ARB, Beta blockers)

Question 4

What anthracycline do you use if you a patient has mild heart disease and really needs an anthracycline

Answer 4

Dexrazoxone

Question 5

What is the MOA of cardiotoxicity with Trastuzumab (HER2 blocker)
Reversible/irreversible?

Answer 5

NRG1 binds to human epidermal growth factor receptor 4 –> causes heterodimerization of HER-2 (activates it)

• HER-2 plays a role in cardiac growth, survival and response to stress
• blocking prevents this from happening

Reversible

Question 6

What are risk factors for trastuzumab cardiotoxicity (7)

Answer 6

• Age 60+
• high BMI 25+
• Alcohol
• Low baseline LVEF
• Prior anthracycline use
• HER-2 polymorphisms
• Hypertension meds

Question 7

What LVEF criteria do we need to stop the HER2 therapy (trastuzumab) (2)

Answer 7

LVEF reduction of 20%+ or LVEF under 50%

Question 8

How often do we have to monitor cardiac function if being treated for monoclonal AB and previously treated with anthracycline

Answer 8

Every 12 weeks

Question 9

What cardiotoxicity does VEGF display? MOA?

Answer 9

Hypertension
- Blocking VEGF leads to vasoconstriction (by reducing NO synthesis)

Question 10

What to do if patient is hypertensive and wanting to start VGEF (not on any anti-hypertensive meds)
What is the step up therapies

Answer 10

1. Amlodipine 5mg (CCB) 3-7 days
2. Add ACE inhibitor or ARB
3. Add indapamide
4. Consider increasing dose of 1+ antihypertensive drug
   +/- add low dose spironolactone (if normal renal function and K+ < 4.5)
   +/- refer to a clinical

Question 11

What to do if patient starting VGEF has..
QT prolongration
cardiac ischemia/dysfunction
Thrombosis/hemorrhage

Answer 11

cardiac ischemia/dysfunction
- suspend therapy

Thrombosis/hemorrhage
- no real evidence to manage, monitor

Question 12

What cardiotoxicity do Tyrosine kinase inhibitors especially sunitinib, Pazopanib
Treatment?
When do you hold drug?

Answer 12

QT prolongation
- Baseline ECG, repeats 2-4 weeks and every 3 months
- avoid QTc prolonging drugs

Hold if:
- QTc > 500msec or rise of 60+ msec from baseline

Question 13

What cardiotoxicity does fluorouracil cause? How does it present

Answer 13

Coronary vasospasm

Presents as angina-like chest pain with possible ECG changes

Question 14

What is the treatment for coronary vasopasms with fluorouracil?
Rechallenge or d/c?

Answer 14

• Hold causative agent
• Administer nitrates and/or CCB
• ECG monitor

May be able to restart therapy with nitrates/CCBs as secondary prophylaxis

Question 15

What cardiotoxicity do BTK inhibitors (ibrutinib) cause

Answer 15

Atril fibrillation

Question 16

Treatment for afib with BTK inhibitors?

Answer 16

Usually use rate control beta blockers

Assess risk using CHADS2-VASc to see if DOACs need to be used
- used cautiously at a reduced dose

Question 17

When are BTK inhibitors temporarily stopped? (2)

Answer 17

Uncontrolled afib
OR
Bleeding

Question 18

What other drugs cause QTc prolongation (5)

Answer 18

ALK inhibitors
Ribociclib (CDK 4/6i)
Osimertinib (EGFRi)
Lapatinib (HER1/EGFRi)

Subitinib and Vandetenib (Multi TKIs)

Question 19

What cardiotoxicity do carfilzomib (proteasome inhibitor) cause
Treatment?

Answer 19

Drop in LVEF

Treatment:
- monitor closely

Question 20

What do immune checkpoint inhibitors cause?
Treatment?

Answer 20

autoimmune cardiomyopathy
- present as acute cardiac failure

Treatment
- DISCONTINUE causative agent
- Initiate HIGH-DOSE corticosteroids

Question 21

When does the highest risk of VTE occur during diagnosis

Answer 21

First 3 months

Question 22

T/F Patients with cancer have a relatively high risk of recurrent VTE despite anticoagulation

Answer 22

True

Question 23

What are risk factors for cancer-associated VTE

Answer 23

Patient related
- Age, obesity, hypertension

Cancer related
- site of cancer (prostate, colon, breast, ovary, lung, pancreas)
- Advanced (metastatic)
- Initial 3 months

Treatment related

Biological
- elevated platelet pre-chemi
- tumour associated pro-coagulants

Question 24

What is the MOA of cancer associated thrombosis

Answer 24

• Sometimes damage to endothelium due to surgery or the tumour itself.
• Activation of platelets via interleukins.

Question 25

When do we consider VTE prophylaxis in cancer outpatients?

Answer 25

Khorana score of 2-3+ - often not used in real world if ambulatory

Question 26

Which cancer therapy would prompt you to use prophylaxis against VTE? (2) Drugs to use (2)

Answer 26

IMiD (immunomodulator) therapy + corticosteroid Lenalidomide + dex OR Thalidomide + dex ASA in lower risk LMWH in higher risk

Question 27

What did the AVERT trial tell us about Apixaban 2.5mg BID in VTE risk Efficacy Safety

Answer 27

Decreased VTE risk Doubled chance of major bleed

Question 28

What did the CASSINI trial tell us about rivaroxaban 10mg daily in VTE risk Efficacy safety

Answer 28

No difference in efficacy or bleed risk than placebo

Question 29

What do we give for primary prevention of VTE in cancer inpatients

Answer 29

Start on a LMWH until discharge or ambulating - Tinzaparin, Dalteparin - Make sure no bleeding or other contraindications

Question 30

What is the current treatment for cancer associated VTE? Duration?

Answer 30

LMWH for a minimum of 3 months - associated with less bleeding than UFH and OAC Consider lifelong anticoagulation for metastatic disease and receiving chemo

Question 31

For secondary prevention what do trials say about DOACs vs LMWH Efficacy Bleeding

Answer 31

Efficacy - DOACs and LMWH are non-inferior Bleeding - All DOACs cause more NON-major bleeding, and GU bleeds compared to LMWH - Equivalent major bleeds

Question 32

When is LMWH preferred in secondary prevention (6)

Answer 32

- High risk of bleeding - GI cancer (or GI malabsorption) - GUrinary/uterine cancer - Interaction with DOAC - Uncontrolled CINV - Obese, underweight

Question 33

When would we consider DOACs in secondary prevention

Answer 33

If the patient does not meet LMWH preferred criteria - Lower risk patients - Not on a known CYP3A4 - Low incidence of NV - Strongly dislike injection