Targeted therapy

Question 1

Targetedtherapy MOA and fact

Answer 1

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

Question 2

Targeted therapy-induced toxicities

Answer 2

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

Question 3

Pertinent Issues with Targeted Therapies

Answer 3

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

Question 4

Targeted therapy drug class

Answer 4

2 class: Small molecules drugs /monoclonal antibodies

Question 5

Small molecules drugs

Answer 5

BCR/ABL (tyrosine kinase)

EpidermalGrowth Factor Receptors TKIs

Question 6

BCR/ABL (tyrosine kinase)

Answer 6

BCR/ABL (tyrosine kinase)

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

Question 7

Imatinib(Glivec®),

Answer 7

BCR/ABL (tyrosine kinase)

Question 8

Dasatinib(Spyrcel®),

Answer 8

BCR/ABL (tyrosine kinase)

Question 9

Nilotinib(Tasigna®)

Answer 9

BCR/ABL (tyrosine kinase)

Question 10

BCR/ABL (tyrosine kinase) SE

Answer 10

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

Question 11

EpidermalGrowth Factor Receptors TKIs (EGFR (+))

Answer 11

erlotinib, gefitinib,afatinib

Question 12

erlotinib

Answer 12

EpidermalGrowth Factor Receptors TKIs

Question 13

gefitinib

Answer 13

EpidermalGrowth Factor Receptors TKIs

Question 14

afatinib

Answer 14

EpidermalGrowth Factor Receptors TKIs

Question 15

EpidermalGrowth Factor Receptors TKIs

SE

Answer 15

:Dermatological toxicities, GI Side effects (diarrhea)

Question 16

Epidermal Growth Factor Receptors TKIs MOA
Decrease

Increase

Answer 16

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

Increase
- Chemo/radiotherapy sensitivity

Question 17

Dermatological toxicities of EGFR TKI

Answer 17

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

Question 18

Several management principles for EGFR TKI

Answer 18

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

Question 19

We can dispense ________ as prophylaxis when rx with EGFR TKIs

Answer 19

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

Question 20

Anti-microbials

Answer 20

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

Question 21

Corticosteroids and Immunomodulators

Answer 21

Corticosteroids and Immunomodulators

• Hydrocortisone 1% cream

Question 22

Emollients / Skin Protectant

Answer 22

Emollients / Skin Protectant

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

Question 23

Antihistamines

Answer 23

Antihistamines

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

Question 24

Retinoids

Answer 24

Retinoids

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

Question 25

Rituximab SE and tx prevention

Answer 25

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

Question 26

Bevacizumab (Avastin®)

Facts, SE

Answer 26

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

Question 27

Bevacizumab avoid in ____

Answer 27

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

Question 28

Trastuzumab (Herceptin)

Answer 28

Trastuzumab (Herceptin®)

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