Cancer Pharm: Natural Products Flashcards
What is the MOA of the vinca alkaloids, vinblastine, vincristine, and vinorelbine; specific to which phase?
- Inhibit tubulin polymerization by DISRUPTING assembly of microtubules; especially those involved in mitotic spindle
- M-phase specific: results in mitotic arrest in metaphase
AE’s of vinblastine?
- N/V, bone marrow suppression (vin-blast-tine), and alopecia
- Potent vesicant (blistering)
Vinblastine is used for what cancers?
Hodgkin’s and NHL’s, breast, and germ cell cancer
Vincristine is similar to vinblastine but has a higher affinity for what?
Axonal microtubules
What is the dose-limiting AE’s of Vincristine?
- Neurotoxicity –> Peripheral sensory neuropathy manifesting as:
- ANS dysfunction w/ orthostatic hypotension; urinary retention; paralytic ileus or constipation; CN palsies; ataxia; seizures; coma
Which 2 vinca alkaloids are associated with SIADH as potential AE’s?
- Vincristine
- Vinorelbine
List 4 AE’s associated with Vinorelbine?
- N/V
- Transient elevations in LFT’s
- Neurotoxicity
- SIADH
Which vinca alkaloid can be used for pediatric tumors, rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma, and Wilms tumor?
Vincristine
Which 3 natural products work by binding to microtubules and enhancing tubulin polymerization causing cell death; which phase do they work in?
- Paclitaxel, Docetaxel, and Cabazitaxel (Taxanes)
- Work in the M phase
Which 2 natural products are associated with hypersensitivity reactions as AE’s?
- Paclitaxel
- Docetaxel
What are acute vs. delayed dose limiting toxicities associated with Paclitaxel?
- Acute = N/V, hypotension, arrhythmias, hypersensitivity
- Delayed = myelosuppression, peripheral sensory neuropathy
Which form of paclitaxel is NOT associated w/ hypersensitivity rxns, has reduced myelosuppressive effects, and neurotoxicity more easily reversed?
Albumin-bound paclitaxel
What are the acute vs. delayed toxicities assoc. w/ Docetaxel?
- Acute = hypersensitivity
- Delayed = neurotoxicity, fluid retention, myelosuppression w/ neutropenia
Why is Cabazitaxel more useful in treating multi-drug resistant tumors than other taxanes?
Is poor substrate for P-glycoprotein
How does Ixabepilone differ in its MOA from the taxanes?
Microtubule inhibitor that binds directly to β-tubulin subunits on microtubules —> dynamic inhibition of microtubule
One of the benefits of Ixabepilone is due to its activity in tumors with what features?
Resistant tumors w/ tubulin mutations and overexpression of P-glycoproteins
What are 2 unique AE’s of Ixabepilone?
- Hypersensitivity rxns
- Neurotoxicity in the form of peripheral sensory neuropathy
Ixabepilon has been approved for tx of what cancer?
- Metastatic breast cancer as monotherapy
- Or in combo w/ capecitabine
What is the MOA of Eribulin?
Inhibits microtubule function leading to a block in the G2-M phase
Eribulin is used in which cancers; has activity in tumors with what features?
- Metastatic breast cancer
- Has activity in tumors that overexpress P-glycoprotein
What is the MOA of the epipodophyllotoxin, Etoposide?
Forms complex w/ and inhibits activity of topoisomerase II and DNA
What is the MOA of the camptothecins, Topotecan and Irinotecan?
Inhibit activity of topoisomerase I, the key enzyme for cutting and religating single DNA strands –> DNA damage
What are 2 forms of diarrhea which may arise as AE of camptothecins, Topotecan and Irinotecan?
- Early form = occurs within 24-hrs of tx; cholinergic event; tx w/ atropine
- Late form = occurs 2-10 days after tx; can be severe and leads to electrolyte imbalances and dehydration
Which camptothecin, topotecan or irinotecan, is more potent and why?
Irinotecan (prodrug) converted to SN-38 in liver, which is 1000-fold more potent topoisomerase I inhibitor
