Term
| What is targeted therapy? What is a MAB? |
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Definition
Targeted therapy - A drug that required a special eligibility test. Furthermore, a drug that targets a specific biologic pathway or well-defined target
Mono-clonal antibodies are a unique subset of targeted therapies.
MAB: Antibody produced artificially from a cell clone and therefore consisting of a single type of immunoglobulin. Work OUTSIDE cell or on the cell membrane. Given INTRAVENOUSLY. |
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Term
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Definition
- Tyrosine Kinase Inhibitors
- Also known as small molecule inhibitors
- work INSIDE the cells
- most are NIBS
- NIBS are given by mouth (nibble, get it?)
- Other TKI's are given IV (ex: Bortezomib and Temsirolimus) |
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Term
| What is the naming convention for MABS? |
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Definition
1. Proprietary first syllable
2. Target
3. Source
4. -mab stem |
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Term
| In terms of naming conventions, give examples of oncology and non-oncology targets, and examples of sources |
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Definition
Targets (Oncology)
- col --> colon
- gov --> ovary
- tum --> Misc.
Targets (Non-oncology)
- lim --> immune
- vir --> viral
- cir --> cardiovascular
Sources:
- u human
- o mouse
- xi chimeric
- zu humanized |
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Term
| Name the MABS for heme malignancies and their targets........ |
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Definition
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Generic
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Brand
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Target
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Indication (s)
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Rituximab
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Rituxan
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CD20
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NHL
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Gemtuzumab
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Mylotarg
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CD33
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AML
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Alemtuzumab
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Campath
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CD52
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CLL
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Ibritumomab
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Zevalin
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CD20
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NHL
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Tosituzumab
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Bexxar
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CD20
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NHL
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Ofatumumab
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Arzerra
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CD20
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NHL
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*Pneumonic: Real Awesome G's Target Iron |
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Term
| What are the MABS commonly used for solid, not liquid, tumors? |
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Definition
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Generic
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Brand
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Target
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Indication (s)
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Trastuzumab
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Herceptin
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HER2
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Breast
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Bevacizumab
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Avastin
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VEGF
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CRC, NSCLC, breast
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Cetuximab
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Erbitux
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EGFR
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CRC, HN
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Panitumumab
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Vectibix
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EGFR
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CRC
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*Pneumonic: Because these are solid, heavy tumors, we need to HEAV to get read of them! |
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Term
| What are the general class effects of MABS? |
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Definition
- Infusion reactions: hypotension, bronchospasm, angioedema
- Generally pre-medicate with HC, diphenhydramine, and an H2-blocker
- Flu-like syndrome |
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Term
| Name some brand/generic NIBS, their target, and indication. |
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Definition
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Generic
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Brand
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Target
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Indication (s)
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Imatinib
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Gleevec
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Bcr-abl
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Ph+ CML and AML; GIST
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Dasatinib
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Sprycel
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Bcr-abl
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CML resistant/intolerant to imatinib
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Nilotinib
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Tasigna
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Bcr-abl
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CML resistant/intolerant to imatinib
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Term
| Name some MORE NIBS, their targets, and indication.... |
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Definition
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Generic
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Brand
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Target: TK of:
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Indication (s)
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Erlotinib
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Tarceva
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EGFR
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NSCLC, pancreatic
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Sorafenib
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Nexavar
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VEGFR, PDGFR, Raf
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RCC, HCC
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Sunitinib
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Sutent
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>80 receptor kinases!
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RCC, GIST
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Pazopanib
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Afinitor
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VEGF, PDGFR
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RCC
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Lapatinib
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Tykerb
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HER2 and EGFR
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HER2+ metastatic breast cancer
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Term
| What are the general class side effects of NIBS? |
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Definition
- Rash, acne-like
- Rash may in fact be correlated to response with erlotinib
- Diarrhea (usually mild)
- Edema
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Term
| MABS and NIBS can target many different classes of receptors, what is the EGFR/erbB/HER family? |
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Definition
- Epidermal growth factors
- Proto-oncogenes that serve as receptors for and code tyrosine kinase; you can have tyrosine kinase both inside and outside the cell (possibly good for MABS) |
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Term
| MABS and NIBS can target many different classes of receptors, what is the VEGF family? |
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Definition
- Vascular endothelial growth factor
- Recruits blood vessel supply to tumor - angiogenesis |
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Term
| MABS and NIBS can target many different classes of receptors, what is the Proteasome family? |
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Definition
- Multicatalytic enzyme complex in all cells
- Degrades intracellular proteins in a regulated manner, especially those "tagged" by ubiquitin
- Inhibition causes a build-up of toxic waste
- Garbage can of your cell
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Term
| MABS and NIBS can target many different classes of receptors, what is the Raf/mek/erk pathway? |
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Definition
- Raf kinases
- Phosphorylation along this pathway, which is downstream of VEGFR, affects gene expression within the cell nucleus |
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Term
| What is the dosing for the NIBS Dasatinib and Imatinib in various indications? Note: blast crisis, chronic phase, and accelerated phase all have different doses |
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Definition
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Generic
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Indication
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Dose & Schedule
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How Supplied
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Imatinib
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CML in CP
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400 mg PO daily PC
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400 mg and 100 mg tablets
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Imatinib
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CML in AP, BC
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600 mg PO daily PC
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See above
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Dasatinib
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CML in CP
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100 mg PO daily
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20 mg, 50 mg, 70 mg, 100 mg tablets
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Dasatinib
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CML in AP, BC
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70 mg PO BID
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See above
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Term
| What is the dosing for the NIBS Nilotinib and Erlotinib in various indications? |
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Definition
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Generic
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Indication
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Dose & Schedule
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How Supplied
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Nilotinib
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CML in CP, AP
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400 mg PO Q12h AC
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200 mg tablets
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Erlotinib
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NSCLC
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150 mg PO daily AC
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25 mg, 100 mg, 150 mg tablets
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Erlotinib
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Pancreatic
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100 mg PO daily AC with gemcitabine IV
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See above
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Term
| What is the dosing for the NIB lapatinib in various indications? |
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Definition
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Generic
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Indication
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Dose & Schedule
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How Supplied
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Lapatinib
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HER2+ metastatic breast
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1250 mg PO daily days 1-21 AC with
-----------------------
Capecitabine 2000 mg/m2 PO in 2 divided doses PC days 1-14 every 21 days
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250 mg tablets
--------------
150mg and 500 mg tablets
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Term
| What is the dosing for the NIBs Sorafenib and Sunitinib in various indications? Note: renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumor are all indications |
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Definition
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Generic
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Indication
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Dose & Schedule
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How Supplied
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Sorafenib
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RCC, HCC
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400 mg PO BID AC
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200 mg tablets
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Sunitinib
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RCC, GIST
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50 mg PO daily x 4 weeks then 2 weeks off
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12.5 mg, 25 mg, 50 mg tablets
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Term
| What is the most common side effect for EGFR agents? How do we treat it? |
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Definition
- Acneiform rash, may correlate with response
- Radiation appears to delay onset of EGFR rash
- Radiation does not worsen EGFR rash and vice-versa
- Treat initially with bath/shower oil (not soap), tepid water, emollient creams, and avoid sun
Grade 1 - topical anti-acne/anti-rosacea agents; avoid topical/systemic steroids and retinoids
Grade 2 - Grade 1 treatments + topical menthol cream or oral antihistamine and oral tetracycline; avoid isotretinoin
Grade 3 - delay EGFR therapy; add compress w/antiinflammatory solutions, high-dose tetracyclines
Grade 4 - Treat in burn unit; d/c EGFR agents |
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Term
| What treatment is most likely to cause hypertension? How can we resolve this? |
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Definition
- VASCULAR endothelial growth factor receptor (VEGFR) inhibition known to cause hypertension
- Grade 3/4 hypertension needs to be medically managed
- Treat according to JNC-VII
- Bevacizumab and Sunitinib are common offenders
- Counsel patients that 10% need HTN therapy
- If experiencing HTN, diuretics mostly 1st step, but ACEI's have compelling indications for mostly everything, BB are preferred post-MI |
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Term
| What are other metabolic problems a patient on targeted therapy could experience? |
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Definition
- Dyslipidemia and hyperglycemia (Temsirolimus (>30% of patients)
- Hypothyroidism (in 3-4% of Sunitinib patients) |
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