Antimicrotubular agents

Taxanes
Mechanism: bind to microtubules>>↑tubulin polymerization (affects mitosis>>↓M-phase). Resistance to taxanes 2/2 alteration in tubulin, MDR phenotype (P170gp>>↑drug efflux; Cabazitaxel resistant to this P170gp system).
Metabolized in liver, via P450, dose reduction with liver dysfx. All platinum agents ↓ elimination of taxane, therefore if platinum agents given before taxane>> ↑taxane levels and tox (↑myelosuppression) (eg. when using Cis/paclitaxel combination - give paclitaxel first!). All taxanes will cause alopecia and are low emetogenic

Paclitaxel (Taxol)
Tox: Myelosuppression (delayed ~10d), hypersensitivity reaction (due to solvent/vehicle - cremophor, needs premedication with dex, H1/H2 antag), cardiac toxicity (bradycardia and other arrhythmias use with caution in pt with CHF, hx of arrhythmias, MI in past 6mo), peripheral sensory neuropathy (dose dependent, ↑risk if hx of DM, ETOh use, ↓folate and ↓B12). Reduce dose by 20% with severe neuropathy of myelosuppression.

Albumin bound paclitaxel (Abraxane)
Nantotaxole with ↑selective binding to albumin receptors on tumor cells (tumor cells have ↑ albumin receptors). Has solvent/vehicle – polysorbate 80, premed with dex 4mg BID day before, on and after. 
Tox: ↓myelosuppression and ↓/no hypersensitivity, ↑neuropathy comparing with paclitaxel.

Docetaxel (Taxotere)
Stronger than paclitaxel, better CNS penetration and distribution than >paclitaxel.
Tox: Myelosuppression (delayed), fluid retention (premed with dex), maculopapular rash, hand and foot syndrome, nail changes, GI sx, ↓N/V. ↓↓↓ neurotoxicity.

Cabazitaxel
Tox: Myelosuppression, hypersensitivity reaction (due to solvent/vehicle – polysorbate 80, needs premedication with dex, H1/H2 antag).

Vinca alkaloids
Mechanism: Prevent polymerization of tubulin dimers and ↓microtubule formation>>↓formation of the mitotic spindle>>mitotic arrest. Resistance same with taxanes. Metabolized in liver, via P450, dose reduction with liver dysfx esp with liver obstruction. All will cause SIADH.

Vincristine (Oncovin)
Tox: ↑affinity to axonal microtubules>>↑neuropathy sensory most of the time but can present with palsies of any kind, hoarseness, facial droop, SBO, urinary retention, constipation (give bowel regiment). SIADH, vesicant.

Vinblastine
Tox: Myelosuppression, ↓neurotoxicity, SIADH, alopecia, mucositis.

Vinorelbine
Tox: Myelosuppression, ↓↓↓neurotoxicity, SIADH, alopecia, mucositis.

Others

Ixabepilone
Mechanism: binds to beta-tubulin subunit>>↓microtubule fx. No cross resistance to other taxanes in cases with P170 phenotype or with tubulin mutations therefore used in cases of progression over taxanes. Used in rr-metastatic breast ca. Metabolized by liver P450 system, attention to inhibitors and inducers.
Tox: Myelosuppression (delayed ~10d), hypersensitivity reaction (due to solvent/vehicle - cremophor, needs premedication with dex, H1/H2 antag), peripheral neuropathy.

Eribulin
Mechanism: Inhibits microtubule growth >>↓microtubule fx>>G2/M phase arrest.
Tox: myelosuppression, ↑QTc, peripheral neuropathy.

Summarized by Veli Bakalov, MD

Special thanks to Christine Barrett, PharmD

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