Etoposide Phosphate

Trade names:  Toposar®, VePesid®, Etopophos® 

Other name:  VP-16, Etoposide phosphate 

Drug type:  Etoposide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug.  This medication is classified as a "plant alkaloid" and "topoisomerase II inhibitor."  (For more detail, see "How this drug works" section below). 

What this drug is used for: 

• Testicular, bladder, prostate, lung, stomach, and uterine, cancers.  Hodgkin's and non-Hodgkin's lymphoma, mycosis fungoides, Kaposi's sarcoma, Wilm's tumor, rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma, brain tumors. 
• It also may be given as high-dose therapy in bone marrow transplant setting. 

Note:  If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful. 

How this drug is given: 

• In tablet form by mouth. 
• As an infusion into the vein (intravenous, IV), as a short infusion or as a continuous infusion over 24 hours. 
• Etoposide is considered an irritant.  An irritant is a chemical that  can cause inflammation of  the vein through which it is given.  If the medication escapes from the vein it can cause tissue damage.  The nurse or doctor who gives this medication must be carefully trained.  If you experience pain or notice redness or swelling at the IV site while you are receiving etoposide, alert your health care professional immediately.   
• The amount  of etoposide that you will receive and the method it is given depends on many factors, including  your height and weight, your general health or other health problems, and the type of cancer or condition being treated.   Your doctor will determine your dose, schedule and how it will be given. 

Side effects: 

Important things to remember about the side effects of etoposide: 

• Most people do not experience all of the side effects listed. 
• Side effects are often predictable in terms of their onset and duration. 
• Side effects are almost always reversible and will go away  after treatment is complete. 
• There are many options  to help minimize or prevent side effects. 
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication. 
• The side effects of etoposide and their severity depend on how much of the drug is given.  In other words, high doses may produce more severe side effects. 
• The following side effects are common (occurring in greater than 30%) for patients taking etoposide: 
• Low white blood cell count. (This can increase  your risk for infection). 
• Low platelet count (This can increase your risk of bleeding). 

Nadir: Meaning low point, nadir is the point in time between chemotherapy cycles in which you experience low  blood counts. 

Onset: 5-7 days
Nadir: 7-14 days
Recovery: 21-28 days
Hair loss 

Menopause (chemotherapy induced) 

• Loss of fertility.  Meaning, your ability to conceive a child may be  affected by etoposide. Discuss  this issue with your health care provider.   
• Nausea and vomiting (especially at high-doses) 
• Low blood pressure (if the drug is infused too fast) 
• These side effects are less common, meaning they occur in 10-29 percent of patients receiving etoposide: 
• Mouth sores (especially at high doses) 
• Diarrhea (especially at high doses) 
• Poor appetite 
• Radiation recall (see skin reactions) 

Other side effects: 

• Metallic taste during infusion of  drug
• Inflammation at injection site 
• Peripheral neuropathy (numbness in  your fingers and toes) may occur with repeated doses. This  is a rare side effect but can be irreversible.  Report numbness or tingling of feet or hands to your health care provider. 

• There is a slight risk of developing a blood cancer such as leukemia years after taking etoposide.  Talk  to your doctor about this risk. 
• Not all side effects are listed above, some that are rare (occurring in less than 10% of patients) are not listed here.  However, you should always inform your health care provider if you experience any unusual symptoms. 

When to contact your doctor or health care provider: 

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms: 

• Fever of 100.5º F (38º C) or higher, chills (possible signs of infection). 

The following symptoms require medical attention, but are not an emergency.  Contact your health care provider within 24 hours of noticing any of the following: 

• Nausea (interferes with ability to eat and unrelieved with  prescribed medication) 
• Vomiting (vomiting more than 4-5 times in a 24 hour period) 
• Diarrhea (4-6 episodes in a 24-hour period) 
• Unusual bleeding or bruising 
• Black or tarry stools, or blood in  your stools or urine 
• Extreme fatigue (unable to carry on self-care activities) 
• Mouth sores (painful redness, swelling or ulcers) 
• Swelling, redness and/or pain  in one leg  or arm and not  the other 
• Numbness or tingling  in your fingers or toes 
• Yellowing  of the skin or eyes 
• Pain, redness or swelling at the IV site 

Always inform your health care provider if you experience any unusual symptoms. 

Precautions:  

• Before starting etoposide treatment, make sure you tell your doctor about any other medications  you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).   Do not take aspirin, products containing aspirin unless  your doctor specifically permits this. 
• Do not receive any kind of immunization or vaccination without your doctor's approval while taking etoposide. 
• Inform your health care professional if you are pregnant or may be pregnant prior  to starting this treatment. Pregnancy category D (etoposide may be hazardous to  the fetus.  Women who are pregnant or become pregnant must be advised  of the potential hazard to the fetus). 
• For both men and women: Do not conceive a child (get pregnant) while taking etoposide. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy. 
• Do not breast feed while taking  this medication.

Self-care tips: 

• Apply warm compresses if you have any pain, redness or swelling at the IV site, and notify your doctor. 
• Drink at least two  to three quarts of fluid every 24 hours, unless you are instructed otherwise. 
• You may be at risk of infection so try  to avoid crowds or people with colds,  and report fever or any other signs of infection immediately to your health care provider. 
• Wash your hands often. 
• To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day  with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed  with 8 ounces of water. 
• Use an electric razor and a soft toothbrush  to minimize bleeding. 
• Avoid contact sports or activities that could cause injury. 
• To reduce nausea, take anti-nausea medications as prescribed by  your doctor, and eat small, frequent meals.    
• Avoid sun exposure.  Wear SPF 15 (or higher) sunblock and protective clothing. 
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely.  You should discuss this with your doctor. 
• Get plenty  of rest.   
• Maintain good nutrition. 
• If you experience symptoms or side effects, be sure to discuss them with your health care team.  They can prescribe medications and/or offer other suggestions that are effective in managing such problems. 

Monitoring and testing: 

You will be checked regularly by your health care professional while you are taking etoposide, to monitor side effects and check your response to therapy.  Periodic blood work to monitor your complete blood count (CBC) as well as the function  of other organs (such as  your kidneys and liver) will also be ordered by your doctor.     

How this drug works: 

Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue.   "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition.  Cancerous cells lose this ability.  Cancer cells no longer have the normal checks and balances in place that  control and limit cell division.  The process of cell division, whether normal or cancerous cells, is through the cell cycle.  The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division). 

The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division.  Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division.   If the cells are unable to divide, they die.  The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink.  They also induce cell suicide (self-death  or apoptosis). 

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific.  Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific.  The scheduling of chemotherapy  is set based on the type of cells, rate  at which they divide, and the time at which a given drug is likely to be effective.  This is why chemotherapy is typically given in cycles. 

Chemotherapy is most effective at killing cells that are rapidly dividing.  Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The "normal" cells will grow back and be healthy but in the meantime, side effects occur.  The "normal" cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss.  Different drugs may affect different parts of the body. 

Etoposide belongs to a class of chemotherapy drugs called plant alkaloids.  Plant alkaloids are made from plants.  The vinca alkaloids are made from the periwinkle plant (catharanthus rosea). The taxanes are made from the bark of the Pacific Yew tree (taxus).  The vinca alkaloids and taxanes are also known as antimicrotubule agents. The podophyllotoxins are derived from the May apple plant. Camptothecan analogs are derived from the Asian "Happy Tree" (Camptotheca acuminata).  Podophyllotoxins and camptothecan analogs are also known as topoisomerase inhibitors.  The plant alkaloids are cell-cycle specific.  This means they attack the cells during various phases of division. 

• Vinca alkaloids:  Vincristine, Vinblastine and Vinorelbine 
• Taxanes:  Paclitaxel and Docetaxel 
• Podophyllotoxins:  Etoposide and Tenisopide 
• Camptothecan analogs:  Irinotecan and Topotecan 

Topoisomerase inhibitors (such as etoposide) are drugs that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. 

• Topoisomerase I inhibitors:  Ironotecan, topotecan 
• Topoisomerase II inhibitors:   Amsacrine, etoposide, etoposide phosphate, teniposide