Topoisomerase inhibitors, RTK and Growth Factor inhibitors, Hormones, etc (antineoplastics)

Question 1

Etoposide

Answer 1

1. MOA: forms complex with topoisomerase II, results in strand breakage of DNA and cell death, most toxic in S and G2
2. SE: leukopenia, N/V/D, stomatitis, alopecia, allergic rxns, hypotension
3. USe: testicular cancer, oat cell carcinoma of lung

Question 2

Topotecan, Irinotecan

Answer 2

1. MOA: topoisomerase I inhibitors
2. SE: topotecan and Irinotecan: anemia, leukopenia, thromobcytopenia, and neutropenia. Irinotecan: dyspnea, cough, rhinitis, asthenia, fever, pain, HA, back pain, chills, edema, abdominal enlargement
3. Use: topotecan for ovarian cancer, irinotecan has broad spectrum

Question 3

Asparaginase

Answer 3

1. MOA: hydrolyzes asparagine, depriving neoplastic cell, leukemia requires exogenous asparagine (normal cells do not)
2. SE: hypersensitivity rxn, alteration of clotting mechanisms, hyperglycemia due to insulin deficiency, pancreatitis.

Question 4

Imatinib

Answer 4

1. MOA: inhibits Bcr-Abl tyrosine kinase which underlies CML, cause remission in 90% of CML
2. Oral, metabolized by CYP3A4
3. SE: GI symptoms, fluid retention, myelosuppression uncommon, hepatotoxiciy

Question 5

Gefitinib

Answer 5

Inhibits EGFR tyrosine kinase by blocking ATP binidng, third line for non-small cell lung cancer (not very effective).
Diarrhea and rash common

Question 6

Erlotinib

Answer 6

1. MOA: inhibits HER1/EGFR tyrosine kinase
2. SE: rash, anorexia, fatigue
3. USE: second line for non-small cell lung cancer, used w/gemcitabine for pancreatic cancer

Question 7

Cetuximab

Answer 7

1. MOA: binds to epidermal growth factor, blocking signals for cell growth and survival, may also have some direct toxicity against tumor cells.
2. SE: rash, itching, HA, D, anaphylactoid txn
3. Use: IV for head and neck cancer, and EGFR positive colon cancer.
4. Panitumumab is similar, used for colon cancer

Question 8

Bevacizumab

Answer 8

1. MOA: VEGF inhibitor, used for clear-cell carcinoma, glioblastoma, and many solid tumors
2. Use: along with a similar drug (ranibizumab) are injected into the eye for tx of wet macular degeneration
3. SE: HTN and proteinuria not assoc w/renal damage, disk of thromboembolism is doubled, rare vessel injury and bleeding (surgery is delayed due to excess bleeding and impaired wound healing)

Question 9

Sunitinb, Sorafenib

Answer 9

1. MOA: VEGF inhibitors similar to Bevacizumab
2. Sunitinib used for renal cell carcinoma, Sorafenib only drug approved for hepatocellular carcinoma,
3. SE: similar to beavcizumab

Question 10

Prednisone, Dexamethasone

Answer 10

1. Prednisone suppresses mitosis in lymphocytes, used for management of leukemia and lymphoma
2. Dexamethasone: used to reduce radiation treatment induced CNS edema

Question 11

Tamoxifen

Answer 11

1. MOA: estrogen antagonist in breast
2. Therapy of breast cancer, prevention in women w/previous history
3. Kinetics: activated by CYP2D6-interaction w/fluoxetine
4. agonist in uterus, may cause uterine hyperlasia/cancer

Question 12

Anastrozole

Answer 12

Inhibits formation of estrogen, used in tamoxifen resistant breast cancers. Main toxicities are hot flashes and nausea.

Question 13

Trastuzumab

Answer 13

Ab against HER2 protein, only used in pts with HER2 overexpression. Used for metastatic breast cancer. Cardiomyopathy is most serious side effect.

Question 14

Flutamide, Bicalutamide, Nilutamide

Answer 14

Block androgen receptors of androgen sensitive tissues or tumors, used for metastatic prostate carcinoma.