Chemotherapy

 

 

Etoposide (Epipodophyllotoxin)

 

CLASS OF DRUG

PLANT DERIVATION

EXAMPLE

EPIPODOPHYLLOTOXINS

From the mandrake plant (Podophyllum peltatum)

Etoposide (VP-16)

Teniposide (VM-26)

 

Semisynthetic analogs of a natural plant product podophyllotoxin.

Antimitotic agent that binds to tubulin.

Long used by indigenous North Americans.

Initial formulations caused severe systemic toxicities.

Development of semi-synthetic analogues, etoposide and teniposide, allowed for the use of podophyllotoxins in the treatment of AML, NHL, and breast, ovarian, gastric and lung malignancies.

Podophyllotoxins are cell cycle specific and target topoisomerase II. Similar to the camptothecins resistance mechanisms are via down-regulation of topoisomerase II and MDR gene expression.

Etoposide

  • can be given po or IV.
  • Used for many tumors including germ cell tumours, ovarian cancer, small and non-small cell lung cancer, NHL, acute leukemia, Ewings and Kaposi’s sarcoma and neuroblastomas.

 

Summary of Toxicities:

Drug

Toxicity

Special Considerations

Epipodophyllotoxins

Myelosuppression (nadir 7-14 days)

 

Stomatitis

 

Nausea and vomiting

 

Elevated liver function tests

 

Hypotension with rapid infusions

 

Hypersensititivity reactions

 

Secondary Acute leukemia:

    • Short latency period of about 30 months.
    • Poor prognosis.
    • Chromosomal translocations of the MLL gene at chromosome band 11q23.
    • M4 and M5 French-American-British (FAB) Classification morphological subtype (monocytic or myelomonocytic).
    • Cumulative risk of this side effect about 5 - 12 % in children with ALL treated with high doses of these drugs. Less in children with germ cell tumors.

 
  • Concentrations above 0.4 mg/mL may cause  precipitation
  • Not to be infused by rapid IV infusion.  Infuse over at least 30-60 minutes. Monitor BP during infusion

 

 

 

 

 

 

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