Microtubule inhibitors

Question 1

What is the function of Microtubules in healthy cells?

Answer 1

-Cytoskeletal support
-Chromosomal separation during m-phase
Assembly -> disassembly

Question 2

Microtubules are concentrated in which part of the body?

Answer 2

Concentrated in CNS (brain, spinal cord)
->Movement & axonal transport involvement

Question 3

What is the MOA of Taxanes?

Answer 3

-Bind to tubulin, promote microtubule assembly
-Prevent disassembly (M-phase specific)
-> paclitaxel paralyzes

Question 4

What is the brand name of Paclitaxel?

Answer 4

Taxol

Question 5

What is the unique toxicity of Paclitaxel?

Answer 5

-Hypersensitivity reactions to the Cremophor (diluent) in the formulation

-Peripheral Neuropathy

it gets worse with each cycle, starting with numbness (finger, feet)

Question 6

Which premeds are required for Paclitaxel?
!!!

Answer 6

Dexamethasone, diphenhydramnie, H2RA

no benefit but still on the label (probably be on the NAPLEX)

Question 7

What is the purpose of Cremphor in the Paclitaxel formulation?

Answer 7

to make it soluble

Question 8

What has to be considered for the administration of Paclitaxel?

Answer 8

-Special “Taxol” tubing required
-has to be DHEP-free and In-line (0.22 micron) filter

-Vesicant precautions

Question 9

What is the brand name of nab-paclitaxel?

Answer 9

Abraxane

(nab = nanoparticle albumin-bound)

Question 10

What is the benefit of the nab-paclitaxel formulation?

Answer 10

-has greater solubility
-No Cremophor vehicle is required
-No hypersensitivity reaction concern
-No premedication required
-Faster infusion possible (30 minutes)
-better dug delivery to pancreatic cancer

it is not interchangeable with conventional paclitaxel

Question 11

What are the unique toxicities of Docetaxel?

Answer 11

-edema -> use dexamethasone (weird: steroids usually cause edema)

-Hypersensitivity (less common than paclitaxel)
-Peripheral neuropathy (less severe than paclitaxel)

-Greater myelosuppression than paclitaxel

Question 12

What is the brand name of Docetaxel?

Answer 12

Taxotere

Question 13

What is the MOA of Vinca Alkaloids?

Answer 13

Bind to tubulin, prevent microtubule assembly

M-phase specific

Question 14

What is the brand name of Vincristine?
Vinca Alkaloid

Answer 14

Oncovin

Question 15

What are the unique Toxicities of Vinca Alkaloids?

Answer 15

-FATAL if given intrathecal (into the cerebral spinal fluid or CSF)

-Peripheral neuropathy (all agents) -> constipation

-Bone marrow suppression (myelosuppression)
with VinorelBine, vinBlastine, NOT Vincristine (Oncovin)

Question 16

Which of the Vinca Alkaloids don’t cause myelosuppression?

Answer 16

Vincristine (Oncovin)

Question 17

Which anti-cancer drug binds to β–tubulin subunit, promotes, then paralyzes (prevents disassembly) microtubule function?

Answer 17

Ixabepilone (Epithilone B analog)

-Contains Cremophor needs pre-meds: dexamethasone, diphenhydramine, H2RA

Question 18

What is the MOA of Eribulin?

Answer 18

Inhibits microtubule spindle formation and thus polymerization