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Pharmacology & Medical Chemistry II > Exam 3: Lecture 7, Monoclonal Antibodies in the treatment of Cancer > Flashcards

Exam 3: Lecture 7, Monoclonal Antibodies in the treatment of Cancer Flashcards

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1
Q

3 Mechanisms of MABs….

A

Block - molecules cancer cells need to grow
Flag - cancer cells for ID by immune system
Deliver - substances to the cancer cell that may kill it

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2
Q

MAB general comments…

A

most given IV infusion
some can be admin SQ
Some can cause infusion reactions, some pt should be premeditated

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3
Q

standard infusion reactions

A 
Fever/shaking chills
flushing/itching
HR or BP change
Chest, back or abdominal pain
Nausea,vomiting,diarrhea
skin rash
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4
Q

Standard infusion reactions occur within….

A

30 min, 2 hrs but can delay up to 24 hr

most common with 1st/2nd dose and incidence declines

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5
Q

Rituximab îs a….

A

engineered murine/human chimeric monoclonal antibody

1st one approved for cancer

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6
Q

Rituximab MOA

A

Apoptosis
ADCC (Antibody-dependent cell mediated cytotoxicity)
CDC (complement-dependent cytotoxicity)

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7
Q

Rituximab admin

A

1st dose: start at 50 mg/hr, can increase by 50mg/hr every 30 min to max of 400 mg/hr

2nd dose: can do 100mg/hr, increase by 100mg/hr until 400 mg/hr

detectable in serum 3-6 months after last dose

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8
Q

Rapid infusion Rituximab

A

for pt who didn’t experience grade 3/4 infusion-related adverse event during cycle 1, have NHL and BLBCL

used with regimens that include corticosteroid

1st dose = standard dose schedule
subsequent doses 20% over 30 min, then 80% over 1hr

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9
Q

Rituximab black box warnings

A

infusion reactions
Hep B reactivation
Mucocutaneous reactions
PML

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10
Q

examples of Mucocutaneous reactions Rituximab

A

Stevens Johnson syndrome, Lichenoid dermatitis, TEN

Onset 1-13 weeks

D/C for severe reactions

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11
Q

PML is a….

A

rare brain infection with the JC virus that usually causes death/severe disability

no cure/treatment/prevention

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12
Q

How to detect PML

A

Brain MRI
Lumbar Puncture
Signs/Symptoms = focal neurologic deficits

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13
Q

Tumor lysis syndrome usually occurs in patients who have….

A

lymphomas or leukemias taking Rituximab

management - hydration, supportive care, dialysis, correct electrolyte abnormalities

pretreat - fluids and allopurinol

onset 12-24hrs after 1st infusion

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14
Q

Other adverse reactions Rituximab….

A

Myelosuppression
Renal Dysfunction
Do not give live virus vaccine

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15
Q

Rituximab and Hyaluronidase allows for it to be given….

A

via SQ injection in 5-7 min instead of Iv infusion

can only be given after patients have received at least 1 IV treatment

approved for some indications that rituximab approved for

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16
Q

Trastuzumab MOA

A

Binds HER2 receptors and inhibits cellular proliferation

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17
Q

Trastuzumab indications

A

HER2 breast cancer and GI cancer

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18
Q

Trastuzumab admin

A

** Loading dose ** both therapies
Adjuvant therapy - contine to 52 weeks of therapy

Metastatic disease - until progression/toxicity

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19
Q

Trastuzumab Adverse effects

A

Infusion reactions most common (20-40%)
cardio toxicity
myelosuppression
embryo-fetal toxicity

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20
Q

Trastuzumab Premedication:

A

acetaminophen and an antihistamine

for 90 min infusion, glucocortioicd recommended too prior

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21
Q

Trastuzumab Cardiotoxicity

A

reduce Ejection fraction, cause HF
<10% as single drug

anthracyclines can potentiate

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22
Q

Trastuzumab Cardiotoxicity risks

A

concurrent or prior anthracyclines or cyclophosphamide
preexisting cardiac disease
prior radiation therapy
old age, smoking, diabetes, thyroid disorders

23
Q

Trastuzumab and Hyaluronidase combo

A

lets you give drug SB over 2-5 min

24
Q

Hyaluronidase mechanism

A

increased permeability of SQ tissue. effects are reversible and permeability restored within 24-48hrs

25
Q

How many biosimilars of Trastuzumab?

A

5

26
Q

Trastuzumab analog

A

fam-trastuzumab deruxtecan-nxki (enhertu)

Topoisomerase I inhibit attached to antibody. Binds to HER2, internalized and linker breaks and release DXd which causes DNA damage (Top I inhibitors)

good response but ILD-13% (black box warning)

27
Q

Ibritumomab (Zevalin) MOA:

A

serves as carrier for radiation

28
Q

Ibritumomab indication

A

patients previously untreated follicular NHL

29
Q

Ibritumomab Admin Schedule

A

Day 1: 250 mg/m2 rituximab infusion (premed Benadryl/tylenol)
Day 7,8,or 9: 250mg/m2 rituximab infusion (premed Benadryl/tylenol)

Within 4 hrs, give Ibritumomab

30
Q

Ibritumomab Precautions

A

minimize radiation exposure

contraceptives at least 12 months after treatment
wash hands X 3 day
universal precautions for bodily fluids X 3 days

31
Q

Ibritumomab Adverse effects

A

Myelosuppression
* more likely than other MABs*

Infusion + Cutaneous reactions
Delayed radiation damage

32
Q

Bevacizumab MOA:

A

binds to VEGF preventing reaction with cell receptors

33
Q

Bevacizumab Dosing

A

Varies with cancer
ranging 5-15mg/kg IV

1st dose: 90 min
2nd dose: 60min
Later dose: 30 min

34
Q

Bevacizumab Adverse effects

A

Impaired wound healing/wound dehiscence (reopening, 28 day precaution)

GI perforation/fistulae

Hemorrhage

Renal injury, proteinuria

Hypertension, monitor BP
Venous thromboembulsims

35
Q

Bevacizumab contraindicaiton

A

Squarmous cell lung cancer, 31% serious or fatal bleeding

36
Q

How many qbiosimilars of Bevacizumab

A

2

37
Q

Cetuximab (Erbitux)

A

targets EGFR and binds to EGFR w/ higher affinity than natural ligands

leads to blocking of signal transduction, inhibit cell growth and lead to apoptosis

38
Q

K-RAS

A

if have Wt then EGFR works

if have mutated, then doesnt

39
Q

Cetuximab (Erbitux) indications

A

squamous cell carcinoma of Heasd/Neck

K-RAS mutation neg, EGFR expressing colorectal cancer

40
Q

Cetuximab (Erbitux) admin

A

1st dose = loading = 400 mg/m2 over 2hr

max rate @ 10mg/min

subsequent weekly doses at 250 mg/m2 over 1hr

premeditate with diphenhydramine

41
Q

Cetuximab (Erbitux) Adverse effects

A

Infusion reactions

Severe reactions more common in NC,TN,ARK,MI,VA,FL, due to pt in these states making antibody to galactose-a-1.3 galactose

Pulmonary toxicity and skin toxicity (rash)

Cardiopulmonary arrest/sudden death (Head/neck cancer more likely) - monitor Mg,K,Ca

hypomagnesemia

42
Q

Immune Checkpoint inhibitors

A

Newest class of MABs

43
Q

Immune Checkpoint inhibitors MOA generalities

A

T cells may be inhibited by a ligand that binds to a specific receptor on the T cell that limits its activation

Drugs may target specific immune checkpoints that are affected by cancer cells to reduce immune activity

44
Q

Atezolizumab MOA

A

PDL1 binding agent

targets PDL1 to restore anti tumor Cell activity

45
Q

Ipilimumab

A

only Checkpoint inhibitor that doesn’t work on PD1/PDL1

works on CTLA4

46
Q

Nivolumab major change in indication

A

Small cell lung cancer removed

47
Q

Nivolumab admin

A

30 min IV infusion

240 mg every 2 week or 480 mg every 4

48
Q

Nivolumab Adverse effects

A

Infusion reaction

Immune-related adverse effects

49
Q

Pembrolizumab admin

A

30 min Iv infusion

200 mg every 3 week until progression or unacceptable toxicity

up to 24 months in pt w/o disease progression all indications except melanoma

children 2mg/kg (up to 200mg) every 3 week

50
Q

Pembrolizumab adverse effects

A

Infusion reaction
Immune related adverse effects
Embryo-fetal toxicity

51
Q

Immune related adverse effect (IRAE)

A

Most common = fatigue, itching, diarrhea, decreased appetite, rash, dyspnea, constipation, nausea

can happen with any immune checkpoint inhibitors bc can effect normal cells.

52
Q

Immune related adverse effect checklist

A

anytime patient receives medication, checklist going over to see if they’ve experienced anything

53
Q

IRAE more common with….

A

CTLA-4 inhibitors (Ipilimumab)

54
Q

Main treatment of IRAEs?

A

Corticosteroids

Early intervention is key

Pharmacology & Medical Chemistry II (43 decks)

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