Biologic Agents

Question 1

Endings
“mabs”
“nibs”

Answer 1

Mab: monoclonal Ab
Nib: signal transduction inhibitor

Question 2

Interferons (INF)

Answer 2

• MOA: not completely known. Direct antiproliferative and indirect induction of host antitumor mech, inhibit angiogenesis
• Clearance: kidneys
• Use: melanoma
• Toxicity:Flu like syndrome, fatigue/anorexia dose limiting, somnulence, myelosuppression, alopecia

Question 3

IL-2 (Aldesleukin-synthetic IL-2)

Answer 3

• Produced by activated T cells. It increases the proliferation of white blood cells, including cytotoxic T cells and NK cell. IL-2 also facilitates the production of antibodies by B cells to further target cancer cells
• Clearance: renal
• Melanoma, renal cell cancer
• Toxicity: flue like syndrome, vascular leak syndrome (wt gain, arrhythmia, tachycardia, hypotension, ARF, pleural effusion) dose limiting, myelosuppression, hepatotoxicity, neurotoxic

Question 4

BRAF inhibitors (vemurafenib/dabrafenib)

Answer 4

• Targets V600 mutation which activates a tyr kinase which causes constitutive activation of MAPK
• Liver metabolism
• Used in Melanoma
• Vemurafenib Toxicity: cutaneous SCC in 25%, hypersensitivity rxn, skin up to SJS, QTC prolongation, photosensitivity

Question 5

Tyrosine kinase inhibitors (erlotinib, gefitinib, imitanib, lopatinib, sorafenib, sunitinib)

Answer 5

-MOA:inhibitor of EGFR tyrosine kinase which leads to lack of autophosphrylation–>decreased signaling
-liver metabolized
Toxicity for each
1) Erlotinib: puritis/rash/hair changes, diarrhea, pulm toxicity
2) Gefitinib: HTN, rash, asthenia, anorexia, N/V, mucositis, rare GI bleed
3) Imitanib/Lopatinib: limited data
5) sorafenib/sunitinib in VEGF cards

Question 6

EGFR (cetuximab and panitumumab)

Answer 6

• MOA: Anti-EGFR Ab; inhibition of mitogenic and anti-apoptotic signals
• More used with colorectal cancer
  1) Panitumumab:
• 40x normal affinity
• lower reaction rate than cetuximab since fully human Ab
• Toxicity: Skin reactions, infusion syndrome (F/C, urticaria, flushing, HA), pulm toxicity, low Mg, paronychial inflammation
  2) Cetuximab
• 10x normal affinity
• Toxicity: 50% transfusion reaction, same as panitumumab

Question 7

-trastuzumab (Herceptin) targets the human epidermal growth factor receptor 2 (HER-2)

Answer 7

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