Microtubule Inhibitors

Vinca Alkaloids (Vincristine and Vinblastine)

• Mechanism 
  • block microtubule formation 
    • bind to tubulin in M phase
    • prevent polymerization of microtubules
    • prevent formation of mitotic spindle
• Clinical use
  • Hodgkin’s lymphoma
    • part of the MOPP regimen
      • M = mustargen
      • O = oncovin = vincristine brand name
      • Procarbazine
      • Prednisone
  • Wilms’ tumor
  • choriocarcinoma
  • ALL
  • testicular cancer
  • Kaposi’s sarcoma
• Toxicity
  • vincristine
    • neurotoxicity
      • areflexia
      • peripheral neuritis
      • paralytic ileus
  • vinblastine
• myelosuppression

Taxols (Paclitaxel)

• Mechanism
  • block microtubule breakdown 
    • hyperstabilize microtubules in M phase
    • mitotic spindle cannot break down
    • anaphase cannot occur
• Clinical use
  • ovarian cancer
  • breast cancer
• Toxicity 
  • peripheral neuropathy
  • myelosuppression
  • hypersensitivity