Chemotherapy

 

 

Vinca Alkaloids

CLASS OF DRUG

PLANT DERIVATION

EXAMPLE

VINCA ALKALOIDS

Periwinkle plant

Vinblastine

Vincristine

Vindesine

Vinorelbine

 

Vinblastine and vincristine are derived from the periwinkle plant and vindesine and vinorelbine are semisynthetic derivatives of vinblastine.

Cell cycle specific to the M phase. Block mitotic spindle formation and prevent transition from metaphase to anaphase.

Vinca alkaloids and the taxanes are "Antimicrotubule" Compounds. Cytotoxic effect by binding to tubulin, a dimeric protein that polymerizes to form microtubules. Cause disruption of intracellular microtubular system and interfere with vital cell functions like mitosis.

Microtubules are

  • an integral component of the cytoskeleton
  • important in the process of cellular division and replication.

Examples are vincristine, vinblastine, vindesine and vinorelbine.

Given IV (not well absorbed orally).

Resistance to vinca alkaloids is via the MDR gene.

 

Vincristine

  • Most commonly used to treat pediatric cancers - ALL, CML, Hodgkin lymphoma, Wilms tumor, Ewings sarcoma, neuroblastoma, medulloblastoma and rhabdomyosarcoma.
  • Given IV as a brief infusion with metabolism by the liver and biliary excretion. Dosages range from 0.05mg/kg to 2mg/­m2 weekly for children.

Toxicities of the vinca alkaloids:

  • quite distinct from agent to agent.
  • Principal toxicity of vincristine is neurotoxicity.
  • Neutropenia is the main toxicity of the other vinca alkaloids.
  • Other side effects include constipation, SIADH, alopecia, mucositis and vomiting.

 

Accidental intrathecal Vincristine has been given and is FATAL.

For this reason in July 2007, the World Health Organization and other patient safety organizations made recommendations to prevent future incidents.  These include:

  • The labeling of vincristine should include a clear warning label that reads: ‘FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES’
  • Syringes should not be used for vincristine administration
  • Vincristine should where possible be prepared by dilution in small volume intravenous bags (the ‘minibag’ technique), rather than in a syringe, to protect against accidental administration via a spinal route.

 

Summary of Toxicities:

Drug

Toxicity

Special considerations

Vincristine

Significant myelosuppression is very rare

 

Neurotoxicity

  • Dose limiting.
  • Related to total cumulative dose. Peripheral sensory and motor neuropathy with loss of deep tendon reflexes.

 

Foot drop, neuritic pain, jaw pain, vocal cord paralysis, paralytic ileus and constipation.

 
  • Liver dysfunction or concomitant radiation to the liver may enhance toxicity
  • Vesicant – painful tissue damage if extravasation occurs.  Use warm compress to treat.
  • Prophylactic stool softeners are recommended
  • Assess for foot drop prior to administration
  • Most protocols indicate a maximum single dose of 2 mg.

 

A variety of Periwinkle plant:

 

 

Back to top

Next