Targeted therapy Flashcards
Targetedtherapy MOA and fact
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
Targeted therapy-induced toxicities
Targeted therapy-induced toxicities •Dermatologicaltoxicity •Gastrointestinaltoxicity •Pulmonarytoxicity •Hepatotoxicity •Cardiotoxicity •Neurotoxicity •Immunotoxicity
Pertinent Issues with Targeted Therapies
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
Targeted therapy drug class
2 class: Small molecules drugs /monoclonal antibodies
Small molecules drugs
BCR/ABL (tyrosine kinase)
EpidermalGrowth Factor Receptors TKIs
BCR/ABL (tyrosine kinase)
BCR/ABL (tyrosine kinase)
- Imatinib(Glivec®),
- Dasatinib(Spyrcel®),
- Nilotinib(Tasigna®)
Imatinib(Glivec®),
BCR/ABL (tyrosine kinase)
Dasatinib(Spyrcel®),
BCR/ABL (tyrosine kinase)
Nilotinib(Tasigna®)
BCR/ABL (tyrosine kinase)
BCR/ABL (tyrosine kinase) SE
Nausea and vomiting;
dose limiting myelosuppression,
fluid retention,
LFTs increase
EpidermalGrowth Factor Receptors TKIs (EGFR (+))
erlotinib, gefitinib,afatinib
erlotinib
EpidermalGrowth Factor Receptors TKIs
gefitinib
EpidermalGrowth Factor Receptors TKIs
afatinib
EpidermalGrowth Factor Receptors TKIs
EpidermalGrowth Factor Receptors TKIs
SE
:Dermatological toxicities, GI Side effects (diarrhea)
Epidermal Growth Factor Receptors TKIs MOA
Decrease
Increase
Epidermal Growth Factor Receptors TKIs MOA Decrease - Proliferation - Growth factor - Cell Survival - Angiogenesis - Metastasis
Increase
- Chemo/radiotherapy sensitivity
Dermatological toxicities of EGFR TKI
- Dermatological toxicities o Very long eye lash o Pruritus / xerosis o Hair loss o Papulopustular rash o Periungual and nail alterations
Several management principles for EGFR TKI
Several management principles
- Treatments should not interfere with the antitumor effects of EGFR inhibitors
- Management should be achieved with minimal side effects
- Ease of administration with rapid results are mandatory to ensure patient compliance
- Therapies must be tailored to the type of clinical presentation
We can dispense ________ as prophylaxis when rx with EGFR TKIs
Anti-microbials Corticosteroids and immunodulators Emollients / skin protectant Antihistamines Retinoids (last line if rash is bad)
Anti-microbials
Anti-microbials
Minocycline 100 mg OM
Doxycycline 100 mg BD
Clindamycin 1% topical (preferred)
Corticosteroids and Immunomodulators
Corticosteroids and Immunomodulators
- Hydrocortisone 1% cream
Emollients / Skin Protectant
Emollients / Skin Protectant
Urea creams (10-40%)
Ammonium Lactate 12% for scaly areas
Moisturizer twice daily
Zinc oxide (13-40%)
Antihistamines
Antihistamines
Menthol 0.5%, Pramoxine 1% Antihistamines, Doxepin Gabapentin (only if antihistamines fail)
Retinoids
Retinoids
Isoretinoin (low dose 20-30 mg/day) for treatment of rash (last line)
Rituximab SE and tx prevention
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
Bevacizumab (Avastin®)
Facts, SE
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
Bevacizumab avoid in ____
Avoid in patients who are at high risk for bleeds or CNS metastasis; watch hypertension, proteinuria and risk of stroke.
Trastuzumab (Herceptin)
Trastuzumab (Herceptin®)
- HER2/Neureceptor antagonist
- Therapeutic Use: Breast cancer, Gastric Cancer (if HER2+)
- Toxicities: Cardiotoxicity, Hypersensitivity (rare –yet package insert recommends paracetamol premed
