Etoposide is a prescription drug used in the treatment of certain lung and testicular malignancies, as well as having a use in other forms of cancer. The drug is given by mouth or by intravenous injection, and is also known by the brand names Eposin, VePesid, Toposar and VP-16.
What Is Etoposide and Where Does It Come From?
Etoposide is a derivative of podophyllotoxin, a chemical which is found in the stem, rhizomes1 and leaves of Podophyllum peltatum and hexandrum, otherwise known as the American and Himalayan Mayapples or Mandrakes. While podophyllotoxin is more commonly used to treat warts caused by the Human Pappiloma Virus (HPV), converting the compound to produce etoposide makes it more specific towards certain cancer cells.
Mayapple extracts are believed to have been used by natives in both North America and the Himalayas, finding use as laxatives and cholagogues2 respectively. However, in 1947 Hartwell and Shear discovered that the resin of the Mayapple reduced the size of tumours while causing the patient abdominal pain. Investigations led to the isolation of podophyllotoxin as the most effective compound found in the plant, and further developments led to the production of the derivatives etoposide, etopophos and teniposide, all similar compounds.
What Does It Do and Why?
Etoposide works by interfering with the function of the enzyme DNA topoisomerase II, an enzyme responsible for the cutting of DNA to allow it to unknot and untangle, an act which would be impossible if the chain of DNA could not be temporarily broken. An accumulation of knots and tangles due to inhibition of topoisomerase II leads to permanent breaks in the DNA strands, causing the cell to hurriedly repair its DNA before too many strands end up in the wrong places and the wrong chromosomes get stuck together. If the cell is overwhelmed, it will either die or will be incapable of proper cell division.
Risk of Leukaemia
The mechanism by which etoposide disrupts cancer cell growth can also have inadvertent effects on normal cells. While there are the usual side effects associated with chemotherapy3, the drug also leads to an increased risk of developing certain leukaemias. This is due to the way in which the damage caused by the drug can lead to different chromosomes becoming stuck together, even in normal cells. Such translocations can lead to two genes becoming stuck together, thus causing the malfunctioning of the genes involved. Some of the translocations seen to occur in leukaemias have also been known to occur after use of etoposide.
The Side Effects of Etoposide
Contrary to popular belief, all drugs do in fact have a range of other possible effects, as they don't just affect their intended target. This is especially true of etoposide as it targets every cell in your body, with the dose required to kill the patient being just less than that required to kill the tumour cells. The following side effects are therefore sometimes seen:
- Bone marrow toxicity, leading to a depressed immune system.
- Impaired wound healing.
- Alopecia (hair loss) due to damage to the hair follicles.
- Severe nausea, loss of appetite and vomiting.
- Constipation or diarrhoea.
- Unusual tiredness or weakness, sometimes causing difficulty walking.
- Back pain and side pain.
- Pain at site of injection.
- Itchy rashes.
Due to the toxic nature of etoposide, it is important that patients on the drug look out for various warning signs, which indicate that they should notify their doctor immediately:
- Blood in urine or stools4.
- Black, tar-like stools.
- Unusual bleeding or bruising.
- Abnormal bruising or bleeding.
- Rapid heartbeat or profuse sweating.
- Loss of consciousness.
- Shortness of breath, tightness of throat or wheezing.
- Swelling of face or tongue.
- Fever or chills.
When and How is Etoposide Used?
Etoposide is used in the treatment of certain forms of lung, testicular and bowel cancer, and is also used in non-Hodgkin's lymphoma, leukaemia and glioblastoma5. The drug is either given by mouth or slowly by intravenous drip, the latter taking between thirty and sixty minutes. The drug is given slowly intravenously as it is known to lower blood pressure, and the patient's blood pressure is often measured during intravenous infusion.
Etoposide may be given with other anti-cancer drugs as this can increase the survival rate for some cancers. The rationale behind combined therapy is that if a tumour cell develops resistance to one of the drugs, the other(s) will kill it. Also, some drugs are more deadly to cells at the edge of the tumour where the blood supply is good, and need to be combined with drug which kills those inside the tumour.
Should I Be Taking Etoposide?
This is something for a trained professional to decide, as the risks will outweigh the benefits if the drug is taken needlessly. Anti-cancer drugs are not a magical cure-all for all the cancers in the world and each specific cancer needs different treatment, and so etoposide is not the right drug for everyone.