Microtubule inhibitors
Microtubule inhibitors are M-phase-specific cytotoxic drugs: vinca alkaloids (vincristine, vinblastine, vinorelbine) block tubulin polymerization, while taxanes (paclitaxel, docetaxel, cabazitaxel) hyperstabilize the assembled spindle. They treat lymphoma, breast, ovarian, lung, and prostate cancer, dosed by body surface area with premedication for taxane hypersensitivity and an absolute dose cap on vincristine to prevent fatal intrathecal exposure and limit disabling neuropathy.
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What this article covers
- Overview
Microtubule inhibitors are cytotoxic chemotherapy drugs that halt cell division by disrupting the mitotic spindle, active only during M phase of the cell cycle.
- Epidemiology
The class is among the most frequently administered in oncology.
- Risk factors
Preexisting peripheral neuropathy: diabetic or hereditary neuropathy leads to earlier, more severe neurotoxicity with vincristine or a taxane.
- Pathophysiology
Microtubules are polymers of alpha- and beta-tubulin heterodimers, each dimer binding two guanosine triphosphate (GTP) molecules, forming the mitotic spindle, cilia, flagella, and the tracks for axoplasmic transport in neurons.
- Clinical features
Vincristine: dose-limiting sensorimotor axonal neuropathy, autonomic neuropathy with constipation and, in severe cases, ileus, plus jaw pain; myelosuppression is mild, and it is a potent vesicant.
- Differential diagnosis
Alkylating agents (e.g., cyclophosphamide): cross-link DNA and kill regardless of cell-cycle phase; cause hemorrhagic cystitis rather than the neuropathy that defines microtubule inhibitors.
- Diagnosis
What establishes candidacy for treatment: a microtubule inhibitor is appropriate only after histologic diagnosis and staging establish a cancer type with proven agent activity, and a pretreatment…
- Management
First, confirm eligibility, then premedicate: verify neutrophil and platelet counts meet threshold; before a Cremophor-based taxane infusion, give dexamethasone 20 mg IV, diphenhydramine 50 mg IV…
- Complications
Neutropenic fever: nadir 7 to 14 days after a taxane or vinblastine dose, the interval of highest infection risk.
- Prognosis
Efficacy is disease- and regimen-specific rather than uniform across the class.
- Prevention
Cap vincristine at 2 mg per dose regardless of calculated body surface area to prevent overdose.
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