Mitotic Inhibitors

Question 0

Taxanes (3)

Answer 0

Paclitaxel
Docetaxel
Cabazitaxel

Question 1

Vinka alkaloids (3)

Answer 1

Vinicristine
Vinblastine
Vinorelbine

Question 2

Epothilones

Answer 2

Ixabepilone

Question 3

Mitotic inhibitors MOA

Answer 3

Inhibit the essential hyper-dynamic changes in micro tubule structure
Mitotic arrest–> apoptosis

Question 4

Vinka alkaloids MOA

Cell cycle M-phase specific (schedule dependent)

Answer 4

Inhibit microtubule elongation or polymerization
Drug binds where next subunit will bind on microtubule (not on subunit that is suppose to bind)
4-deacetyl is major inactive metabolite

Question 5

Taxanes and Epothilone MOA

Answer 5

Inhibit depolymerization or microtubule shortening

Drug Binds to a specific site on beta tubulin subunit

Question 6

Vinka alkaloids ADR

Answer 6

Severe vesicant/extravasation

intrathecal injection is FATAL BBW only for IV dose

Question 7

Vincristine toxicity

Answer 7

• dose limiting NEUROTOXICITY*

Question 8

VinBlastine toxicity

Answer 8

• dose limiting MYELOSUPPRESSION *

B=bone marrow toxicity

Question 9

VinorelBine toxicity

Answer 9

• dose limiting MYELOSUPPRESSION *

B=bone marrow toxicity

Question 10

Paclitaxel

Answer 10

Formulated 50/50 alcohol and cremophor EL (hypersensitivity rxn) pre-treat pt.
*CYP2C8 (rare DME) to 6-hydroxypaclitaxel (major, less active metabolite)
Toxicity: *peripheral neuropathy

Question 11

Abraxane

Answer 11

Albumin bound paclitaxel: shell forms nano particles better taken up by cancer cells.
*Does NOT cause hypersensitivity rxn)
*DO NOT interchange formulation w/ paclitaxel bc mor drug is delivered to cells w/ Abraxane
Toxicity: peripheral neuropathy

Question 12

Docetaxel

Answer 12

• Formulated w/ polysorbate 80-> hypersensitivity rxn possible pre treat pt.
  CYP3A4 metabolism to hydroxydocetaxel (major metabolite)
  Toxicity: fluid retention, myelosuppression w/neutropenia, and peripheral neuropathy

Question 13

Cabazitaxel

Answer 13

*Formulated w/ polysorbate 80-> hypersensitivity rxn, pretreat pt.
lower affinity for P-gp: drug used for docetaxel-resistant metastatic breast cancer
CYP3A4/5 metabolism to several des- and didesmethyl active metabolites
Toxicity: (end metabolite is still active so there are a lot of toxicities) neutropenia (dose limiting), peripheral neuropathy, diarrhea

Question 14

Ixabepilone (an epothilone)

Answer 14

lacks P-gp affinity

Toxicity: neutropenia, peripheral neuropathy, hypersensitivity rxn (formulated w/cremophor

Question 15

Mechanism of resistance to mitosis inhibitors

Answer 15

Vinca alkaloids: mutant p53 oncogene (cell makes protein products not responsive to vinca alkaloids)
Taxanes: P-gp mediated drug efflux