Cancer treatment - traditional chemotherapy - antimicrotubule agents (1)

Question 1

2 drug classes that inhibit microtubules and what is the difference between them in MOA?

Answer 1

Taxanes and vinca alkaloids

Microtubules undergo de-polymerization (into tubulin dimers) and polymerization (back into microtubule form) - this is a dynamic process

Taxanes inhibit de-polymerization - leaving them in microtubule form … microtubulin stabilizers

Vinca alkaloids inhibit polymerization - leaving them in tubulin dimer form … microtubulin disruptors

Microtubules are important for cell division, so if they are locked in either of these forms, it will prevent cell division from occuring

Question 2

Are tubulin binding agents cell cycle specific or non specific?

Answer 2

Cell cycle specific - specific to the m phase (mitosis / division phase)

Because they lock the microtubule in polymer or dimer form, prevent cells from dividing (which occurs during the m phase) … cells will be stuck in the m phase (unable to divide)

Question 3

Which 2 drugs are taxanes?

Answer 3

Paclitaxel
Docetaxel
(microtubulin stabilizers)

Question 4

Which taxane is more potent?

Answer 4

Docetaxel is more potent than paclitaxel

Question 5

Paclitaxel pre treatment

Answer 5

Made in castor oil, so hypersensitivity can occur
Should be pretreated with…
-dexamethasone at 12 and 6 hours pre infusion
-diphenhydramine and H2 antagonist (famotidine) 30 minutes prior to infusion

Question 6

Paclitaxel has an interaction with which other chemo drug? How is this managed?

Answer 6

Cisplatin
-cisplatin impairs the clearance of paclitaxel
-paclitaxel must be given FIRST

Question 7

Docetaxel pre treatment

Answer 7

Pre treatment is required to prevent capillary leak syndrome and hypersensitivity reactions
-dexamethasone PO x 3 days - day before, day of, and day after infusion

Question 8

What is the dose limiting toxicity of paclitaxel vs docetaxel

Answer 8

Paclitaxel - peripheral neuropathy

Docetaxel - myelosuppression

Question 9

Docetaxel specific ADRs (3)

Answer 9

Full body hair loss (not just on head)
Nail changes (recommend patients get manicures to maintain and clean dead parts)
Fluid retention

Question 10

Paclitaxel specific ADRs (2)

Answer 10

Arthralgias
Myalgias

Question 11

Which 3 drugs are vinca alkaloids

Answer 11

Vincristine
Vinblastine
Vinorelbine
(remember these are microtubule disruptors)

Question 12

Vincristine has limited _____________

Answer 12

Myelosuppression

Question 13

Vinblastine has limited _______________

Answer 13

Neurotoxicity

Question 14

Vinca alkaloid administration consideration

Answer 14

These drugs can NOT be given IT (intrathecally) - can be fatal

Question 15

Vincristine dose limiting toxicity

Answer 15

Peripheral neuropathy
-dose cap of 2 mg as a result (no dose caps for the other 2 vinca alkaloids)

Question 16

Limiting toxicity of vinblastine and vinorelbine

Answer 16

Myelosuppression