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Temozolomide

Temozolomide

Definition

A chemotherapy medicine used to reduce the size of a cancerous tumor and prevent the growth of new cancer cells. In the United States, temozolomide is known by the brand name Temodar and in the European Union as Temodal.

Purpose

Temozolomide is used as a treatment for a type of brain tumor called an anaplastic astrocytoma . Specifically, it is a treatment for patients who have experienced a relapse (or recurrence) of this disease while being treated with the drug procarbazine , one of a group of anti-cancer drugs known as nitrosoureas, which include carmustine and lomustine . As of 2001, it is being investigated as a treatment of newly diagnosed and advanced stages of other brain/central nervous system tumors, such as oligodendrogliomas and ependymomas, and for an advanced malignant melanoma that has spread to the central nervous system.

Description

Temozolomide was first made in a British laboratory in the early 1980s and was approved for use in the United States in 1999.

It is included in the cancer drug category termed antineoplastic agents . These drugs slow or prevent the growth of cancerous tumors. Temozolomide is among a subset of antineoplastic agents that were designed to target rapidly-dividing cells in the body, such as the cancerous cells that form tumors. These drugs work by altering the structure of the DNA in fast-growing cells, causing a cell to die or to fail to replicate itself.

The use of temozolomide as a treatment for cancers other than brain cancer and in combination with different cancer therapies is still experimental. Many ongoing clinical trials focus on the use of temozolomide as a cancer treatment not only for newly diagnosed and recurrent brain/central nervous system tumors, but also for advanced stages of germ cell tumors , lung cancer (non-small cell), mycosis fungoides , Sézary syndrome , and gastrointestinal cancers . Some clinical trials also involve experimental treatment of advanced brain cancer or malignant melanomas using a combination of temozolomide and other cancer drugs or therapies, such as radiation therapy and the drugs interleukin-12, aldesleukin , thalidomide , carmustine, interferons , and lomustine.

It is not yet known if temozolomide is more effective than other treatments, but it has been shown to stop or slow disease progression in patients with recurrent brain tumors who have not responded to other treatments, including other chemotherapy drugs, radiation therapy, or surgery. However, the duration of the response varies.

For the treatment of a malignant melanoma, temozolomide is as equally effective as dacarbazine , the drug most frequently used for this cancer. If the cancer spreads to the central nervous system, temozolomide may be more effective than dacarbazine, because it, unlike dacarbazine, is able to move from the blood into the central nervous system.

A possible advantage to the use of temozolomide over other therapy options is that a patient may be able to continue the treatment over a longer period of time. Decreased bone marrow activity (myelosuppression) is a common reaction to many chemotherapy drugs, including temozolomide. But unlike other drugs, this condition is temporary in temozolomide patients; therefore, patients can physically tolerate a more extended treatment. Also, the side effects experienced with temozolomide are usually less severe compared to other drug treatment options, resulting in patients with a better quality of life.

Recommended dosage

Temozolomide is available in capsules and is taken orally. Dosage is determined based on a patient's body height and weight. The typical dose for the first treatment cycle is 150 mg per day taken for five consecutive days, with each treatment cycle lasting 28 days. The number of treatment cycles depends on how well a patient tolerates the treatment and its effectiveness in treating the cancer. The optimal number of treatment cycles is not known.

Because myelosuppression is a common reaction to this drug treatment, white blood cell and platelet counts are carefully monitored, particularly in the first few treatment cycles. A complete blood count is made on day 22 and day 29 of a treatment cycle. If blood counts are below a certain level, treatment is either postponed or the dosage is decreased in the next treatment cycle. The minimum recommended dosage is 100 mg. Blood counts within an acceptable range can result in an increased dosage for the next cycle.

Precautions

Food decreases the rate at which temozolomide is absorbed into the bloodstream. Although there are no foods that should be avoided while taking this drug, it should be taken on an empty stomach and swallowed whole with a glass of water.

Side effects

The most common side effects for patients treated with temozolomide are nausea and vomiting , headache, fatigue , and constipation. In a study of 158 brain tumor patients, 53% experienced nausea and 42% experienced vomiting, and most of these cases were moderate, with only about 10% of the patients experiencing severe forms of either condition. Avoiding food prior to taking temozolomide can decrease the occurrence of these effects, or they can be controlled with medication. In the same study, 41% of the patients reported headaches, 34% reported feeling fatigued, and 33% experienced constipation.

Between 10% and 20% of the patients in the study experienced convulsions, partial paralysis, diarrhea , fever , feeling weak, a infection, dizziness, coordination problems, a memory change , or insomnia. Less than 10% of the 158 patients experienced anorexia , rash or itching , inflammation in the throat region, incontinence , back pain, an overactive adrenal gland, anxiety, comprehension problems, coughing, muscle pain, weight gain, depression , sinus problems, or abnormal vision.

Myelosuppression is experienced by 4% to 19% of patients. Neutropenia and thrombocytopenia are the most common forms, and the more severe cases of both are higher in women and in the elderly (patients older than age 70) than in men. When myelosuppression occurs, it usually appears late in the first few treatment cycles and does not worsen over time. On average, blood count levels return to normal 14 days after the lowest blood count is recorded.

Coping with side effects may require making some lifestyle changes or, in some cases, taking medication. For example, to treat constipation, patients may be told to increase the amount of fluid they drink, perform regular exercise, and eat more dietary fiber, while any infection will require medication. Treatment options for side effects should be discussed with a doctor.

Interactions

Valproic acid, a drug used to treat seizures, decreases the clearance of temozolomide from the body by about 5%. No other negative drug interaction has been reported, although its interaction with many conventional and alternative drugs has yet to be studied.

See Also Cancer genetics; Chemoprevention; DNA cytometry; Drug resistance; Vaccines

Monica McGee, M.S.

KEY TERMS

Anaplasia

Characteristics of a cell, such as shape and orientation, that make it identifiable as a cancer cell.

Anaplastic astrocytoma

The advanced stage of a rapidly growing brain tumor. This type of tumor originates in the brain, unlike other brain tumors that may occur due to the spreading of cancer from another part of the body.

DNA (Deoxyribonucleic acid)

The genetic material found in each cell in the body that plays an important role in controlling many cell functions. When a cell divides to create two new cells, an identical copy of its DNA is found in each. If there is an error in a cell's DNA, division may not occur.

Drug clearance

The amount of a drug that is removed from the body through urination.

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