Millikan IHO Week 3

Question 1

anti-tubulin, small, epithelial malignancies, especially breast and ovarian

Answer 1

Paclitaxel

Question 2

topisomerase inhibitor, small, breast cancer, lymphoma

Answer 2

Doxorubicin

Question 3

topoisomerase inhibitor, small, germ cell tumors, lymphoma

Answer 3

Etoposide

Question 4

proteosome inhibitor, small, multiple myeloma, mantle cell lymphoma, Waldenstroms (a type of non-hodgkin lymphoma)

Answer 4

Bortexomib

Question 5

active metabolite (SN-38) can be liberated by ubiquitous hydrolytic enzymes in/outside of cells; in the liver oxidized by several different P-450 members and conjugated to sugars to bile to excreted; gut flora can convert back to SN-38

Answer 5

Irinotecan (in the family of Camptothecins)

Question 6

4 Pharmacologic Points for Irinotecan

Answer 6

1. inhibits the re-ligation step of Topo1 activity 2. prodrug of SN-38 and relies on intact lactone 3. effort to make analogs with improved TI 4. now formulated in 2 ways

Question 7

3 Clinical Points for Irinotecan

Answer 7

1. GI cancers including the pancreas 2. DLT is diarrhea 3. neutropenia is not cumulative and the drug can be given for extended time (>1yr)

Question 8

What causes intercalation into DNA (pi stacking)

Answer 8

Doxorubicin

Question 9

What causes most of the toxicity in use of Doxorubicin

Answer 9

generation of ROS and blocking of Topo 2

Question 10

What do you give to help prevent Doxorubicin toxicity

Answer 10

Iron Chelators

Question 11

4 Clinical Points for Doxorubicin

Answer 11

1. broad spectrum anti-cancer activity 2. DLTs are stomatitis and myelosuppression 3. cardiac damage 4. nasty vesicant

Question 12

broad spectrum anti-cancer drug essential for small cell carcinoma of lung and germ cell tumors and (aggressive lymphomas)

Answer 12

Etoposide

Question 13

Causes acute leukemia at 1-2 per thousand at 2-3 yr latency, rapidly fatal, DLT is myelosuppression

Answer 13

Etoposide

Question 14

Work by inhibiting tubulin polymerization and thereby causing mitotic arrest

Answer 14

Vinca alkaloids

Question 15

Dose limiting toxicity of Vinca Alkaloids

Answer 15

neuropathy

Question 16

What is not very myelosuppressive and is added to many regimens

Answer 16

Vincristine

Question 17

What is extremely constipating

Answer 17

Vinblastine

Question 18

What works by binding to inner surface of microtubules where GDP binds the beta-subunit and stabilizes the structure, preventing depolymerization

Answer 18

Taxanes

Question 19

Dose limiting toxicity of the Taxanes

Answer 19

Neuropathy

Question 20

Most common chemotherapy for solid tumors combination?

Answer 20

carboplatin and paclitaxel

Question 21

What binds to the positive end of microtubule preventing elongation (doesn’t seem to work)?

Answer 21

Eribulin

Question 22

Drug that causes myelosuppression and is dose-limiting and neuropathy

Answer 22

Eribulin

Question 23

If can’t feel feet think what category of cancer med?

Answer 23

Anti-microtubule agent (Paclitaxel)

Question 24

What blocks the 26S proteasome proteolytic activity (a threonine protease) given IV or subq

Answer 24

Bortezomib

Question 25

Dose limiting effects of Bortezomib?

Answer 25

fatigue, neuropathy and myelosuppression

Question 26

Extremely important in myeloma and other B-cell malignancies

Answer 26

Bortezomib