Targeted therapy Flashcards

1
Q

Targetedtherapy MOA and fact

A

Targeted therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression

The development of targeted therapies requires the identification of good targets

FDA considers targeted therapy as a drug with a reference to a diagnostic test that must be performed for the patient to be eligible to receive the drug

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2
Q

Targeted therapy-induced toxicities

A
Targeted therapy-induced toxicities
•Dermatologicaltoxicity 
•Gastrointestinaltoxicity 
•Pulmonarytoxicity 
•Hepatotoxicity 
•Cardiotoxicity 
•Neurotoxicity 
•Immunotoxicity
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3
Q

Pertinent Issues with Targeted Therapies

A

Patient Education Issues
•Drug adherence?
•Significance of food consumptions

Long-term toxicities
•Unknown; most drugs are only out of the market for less than a decade
•Pharmacovigilance

Toxicity and Response Issues: Pharmacogenomicand Biomarkers

Financial Burden

Drug-drug interactions

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4
Q

Targeted therapy drug class

A

2 class: Small molecules drugs /monoclonal antibodies

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5
Q

Small molecules drugs

A

BCR/ABL (tyrosine kinase)

EpidermalGrowth Factor Receptors TKIs

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6
Q

BCR/ABL (tyrosine kinase)

A

BCR/ABL (tyrosine kinase)

  • Imatinib(Glivec®),
  • Dasatinib(Spyrcel®),
  • Nilotinib(Tasigna®)
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7
Q

Imatinib(Glivec®),

A

BCR/ABL (tyrosine kinase)

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8
Q

Dasatinib(Spyrcel®),

A

BCR/ABL (tyrosine kinase)

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9
Q

Nilotinib(Tasigna®)

A

BCR/ABL (tyrosine kinase)

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10
Q

BCR/ABL (tyrosine kinase) SE

A

Nausea and vomiting;
dose limiting myelosuppression,
fluid retention,
LFTs increase

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11
Q

EpidermalGrowth Factor Receptors TKIs (EGFR (+))

A

erlotinib, gefitinib,afatinib

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12
Q

erlotinib

A

EpidermalGrowth Factor Receptors TKIs

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13
Q

gefitinib

A

EpidermalGrowth Factor Receptors TKIs

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14
Q

afatinib

A

EpidermalGrowth Factor Receptors TKIs

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15
Q

EpidermalGrowth Factor Receptors TKIs

SE

A

:Dermatological toxicities, GI Side effects (diarrhea)

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16
Q

Epidermal Growth Factor Receptors TKIs MOA
Decrease

Increase

A
Epidermal Growth Factor Receptors TKIs MOA
Decrease 
-	Proliferation 
-	Growth factor 
-	Cell Survival 
-	Angiogenesis 
-	Metastasis 

Increase
- Chemo/radiotherapy sensitivity

17
Q

Dermatological toxicities of EGFR TKI

A
-	Dermatological toxicities 
o	Very long eye lash 
o	Pruritus / xerosis 
o	Hair loss
o	Papulopustular rash 
o	Periungual and nail alterations
18
Q

Several management principles for EGFR TKI

A

Several management principles

  1. Treatments should not interfere with the antitumor effects of EGFR inhibitors
  2. Management should be achieved with minimal side effects
  3. Ease of administration with rapid results are mandatory to ensure patient compliance
  4. Therapies must be tailored to the type of clinical presentation
19
Q

We can dispense ________ as prophylaxis when rx with EGFR TKIs

A
Anti-microbials
Corticosteroids and immunodulators 
Emollients / skin protectant 
Antihistamines 
Retinoids (last line if rash is bad)
20
Q

Anti-microbials

A

Anti-microbials
Minocycline 100 mg OM
Doxycycline 100 mg BD
Clindamycin 1% topical (preferred)

21
Q

Corticosteroids and Immunomodulators

A

Corticosteroids and Immunomodulators

  • Hydrocortisone 1% cream
22
Q

Emollients / Skin Protectant

A

Emollients / Skin Protectant

Urea creams (10-40%)
Ammonium Lactate 12% for scaly areas
Moisturizer twice daily
Zinc oxide (13-40%)

23
Q

Antihistamines

A

Antihistamines

Menthol 0.5%, 
Pramoxine 1% 
Antihistamines, 
Doxepin 
Gabapentin (only if antihistamines fail)
24
Q

Retinoids

A

Retinoids

Isoretinoin (low dose 20-30 mg/day) for treatment of rash (last line)

25
Q

Rituximab SE and tx prevention

A

Rituximab (Mabthera®)

Infusion-related reactions (fever, chills/rigors, bronchospasm, hypotension)
- First infusion is known to be associated with higher incidence of infusion-related reactions
- Premedicate with paracetamol and diphenydramine
- Close monitoring for reactions
- Start infusion slow and increase rate over time
o Subsequent cycles can benefit from shorter infusion (90 minutes) if the patient does not experience any infusional reaction in his/her first cycle of treatment
- Prompt treatment & other supportive measures if reactions
Nausea and vomiting, infection and myelosuppression are uncommon

26
Q

Bevacizumab (Avastin®)

Facts, SE

A

Bevacizumab (Avastin®)

  • Vascular Endothelial Growth Factor Inhibitor
  • No premedications required.
  • Avoid in patients who are at high risk for bleeds or CNS metastasis; watch hypertension, proteinuria and risk of stroke.

SE

  • Hemorrhage -avoid or discontinue use in patients with serious hemorrhage (e.g. hemoptysis, brain hemorrhage)
  • Increased risk of thrombotic events (e.g. stroke, MI)
  • Wound healing complications -stop at least 28 days before & after surgery or until wound is fully healed
  • Gastrointestinal perforations (abdominal pain, N/V, constipation, and fever)
    •Discontinue in patients with suspected gastrointestinal perforation
  • Proteinuria
    o Monitor urine protein
    o Temporarily suspend if moderate proteinuria
    o Discontinue in nephrotic syndrome
27
Q

Bevacizumab avoid in ____

A

Avoid in patients who are at high risk for bleeds or CNS metastasis; watch hypertension, proteinuria and risk of stroke.

28
Q

Trastuzumab (Herceptin)

A

Trastuzumab (Herceptin®)

  • HER2/Neureceptor antagonist
  • Therapeutic Use: Breast cancer, Gastric Cancer (if HER2+)
  • Toxicities: Cardiotoxicity, Hypersensitivity (rare –yet package insert recommends paracetamol premed