Etoposide
Encyclopedia
Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting. Unlike enzyme inhibitors, it exploits the normal mechanism of action of the enzyme
topoisomerase II, which aids in DNA unwinding, and by doing so causes DNA strands to break. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. It is used as a form of chemotherapy
for cancers such as Ewing's sarcoma, lung cancer
, testicular cancer
, lymphoma
, non-lymphocytic leukemia
, and glioblastoma multiforme
. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow
or blood stem cell transplant.
Its chemical make-up derives from podophyllotoxin
, a toxin found in the American Mayapple
.
The name VP-16 likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologistHartmann F. Stähelin
.
as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.
In general, patients are advised to call their doctor in case of fever
, symptoms of infection
or painful injection sites, as these may progress severely without adequate medical attention.
Patients are advised to drink large amounts of fluids after treatment to prevent damage to the bladder
and kidney
s, typically 1.5 to 3.5 litres of water
on the day of treatment and for several days after.
Less common are:
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
topoisomerase II, which aids in DNA unwinding, and by doing so causes DNA strands to break. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. It is used as a form of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
for cancers such as Ewing's sarcoma, lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
, testicular cancer
Testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...
, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, non-lymphocytic leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, and glioblastoma multiforme
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...
. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
or blood stem cell transplant.
Its chemical make-up derives from podophyllotoxin
Podophyllotoxin
Podophyllotoxin , otherwise known as podofilox, is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species. Under the trade name Condylox, a topical gel, it is used on the skin to treat external genital warts, caused by some types of the human papillomavirus...
, a toxin found in the American Mayapple
American Mayapple
Podophyllum peltatum, commonly called mayapple , is a herbaceous perennial plant in the family Berberidaceae, native to wooded areas of eastern North America.The stems grow to 30-40 cm tall, with 2 or occasionally 3 palmately lobed...
.
The name VP-16 likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologistHartmann F. Stähelin
Hartmann F. Stähelin
Hartmann F. Stähelin, M.D. was a Swiss pharmacologist with an outstanding record in basic and applied cancer and immunology research. He discovered two important drugs: etoposide and ciclosporin.-Early life:...
.
Mechanism of Action
Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, preventing re-ligation of the DNA strands. This causes errors in DNA synthesis and promotes apoptosis of the cancer cell.Administration
It is given intravenously or orally in capsule form. If the drug is given by IV it must be done slowly over a 30 to 60 minute period because it can lower blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.
In general, patients are advised to call their doctor in case of fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, symptoms of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
or painful injection sites, as these may progress severely without adequate medical attention.
Patients are advised to drink large amounts of fluids after treatment to prevent damage to the bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, typically 1.5 to 3.5 litres of water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
on the day of treatment and for several days after.
Side-effects
Common are:- low blood pressureHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
- hair lossAlopeciaAlopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
- pain and or burning at the IV site
- constipationConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
or diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and... - metallic food tasteParageusiaParageusia is the medical term for a bad taste in the mouth.One common form of parageusia is a metallic taste of food. This can be a side effect of several medications, such as acetazolamide, eszopiclone, zopiclone, metronidazole, or etoposide....
- Bone marrowBone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
suppression, leading to:- decreased white blood cellWhite blood cellWhite blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
counts (leading to increased susceptibility to infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s) - low red blood cellRed blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
counts (anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
) - low plateletPlateletPlatelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
counts (leading to easy bruising and bleeding)
- decreased white blood cell
Less common are:
- nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting - allergic type reactions
- rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
- feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, often occurring shortly after IV administration and not due to infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease... - mouth soresMouth ulcerA mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
- Acute myeloid leukemiaAcute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...