Thiotepa

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Thiotepa

Definition

Thiotepa is a chemotherapy drug used to reduce the size of a cancerous tumor and prevent the growth of new cancer cells. This drug is sometimes referred by the brand name Thioplex.

Purpose

Thiotepa has been used in the treatment of many types of tumors, but it is most often used as a treatment for the advanced stages of breast cancer , ovarian cancer , the middle and late stages of bladder cancer , and to control body cavity effusions, such as pleural effusion and pericardial effusion , that occur with some cancers. It is also sometimes used for the treatment of Hodgkin's disease and other lymph system cancers.

Description

Thiotepa was developed in the 1950s. It has been an approved cancer drug in the United States for over 20 years.

This drug is included in the cancer drug category termed antineoplastic agents , which slow or prevent the growth of cancerous tumors. Specifically, thiotepa is among a group of antineoplastic agents that were designed to alter the structure of the DNA in cells, causing a cell to die or to fail to replicate itself. These drugs do not distinguish between normal and cancerous cells and thus affect both equally.

Thiotepa is among several chemotherapy drugs being investigated for use in experimental high-dose chemotherapy, where a cancer patient is given a combination of several chemotherapy drugs at higher than normal dose levels. This treatment approach has been the focus of numerous clinical trials , most commonly for advanced breast cancer. One high-dose breast cancer chemotherapy treatment uses a combination of thiotepa, cyclophosphamide , and carboplatin . However, based on results from studies dating from 1999 to 2000, the effect of high-dose chemotherapy treatments, including those using thiotepa, have not conclusively improved the outcome or quality of life for breast cancer patients.

One approved chemotherapy treatment for advanced stages of breast cancer, where patients have not responded to other chemotherapy treatments or have experienced a relapse after a chemotherapy treatment, is a combination drug therapy of thiotepa, doxorubicin , and vinblastine . However, the results of this and other treatment options for late-stage breast cancer are not good. Treatment with a combination of chemotherapy drugs results in approximately 10% to 20% of patients showing no signs of cancer, and the duration of this response is usually less than 12 months.

Thiopeta is about as equally effective as the other chemotherapy drugs recommended for treating bladder cancer, including mitomycin-C , doxorubicin, ethoglucid, or epirubicin . Research results suggest that these drugs may reduce the chance for cancer recurrence but has little effect on reducing the metastasis of the disease. After surgical removal of a tumor, thiotepa has been shown to reduce the size of the remaining tumor in 29% of bladder cancer patients.

Body cavity effusions are a known complication for the advanced stages of many cancers, including lung cancer and breast cancer. Fluid in the heart cavity, or pericardial effusion, can be managed with the use of a procedure called a pericardiocentesis and the injection of thiotepa into the cavity. This treatment has been shown to result in the absence of pericardial effusion in approximately 70% to 90% of all cancer patients for at least 30 days. In a 1998 study of 23 cancer patients with pericardial effusion, 83% responded to this treatment, and the condition did not worsen for about nine months.

Recommended dosage

Patients are usually given thiotepa intravenously (directly into the vein) either as a rapid injection or through an intravenous (IV) infusion (drip). It can also be administered as an injection into a muscle or into the fluid that surrounds the spinal cord. For the treatment of body cavity effusions, it is injected through a tube into the site where this condition occurs. In bladder cancer patients, it is instilled directly into the bladder.

Each dosage is calculated based on a patient's weight at the start of each treatment. The correct dosage is carefully matched and adjusted to an individual's overall condition and response to the treatment. There is a range of doses for each method used to administer the drug, and the initial dose is usually the higher value in the range. How well the patient tolerates the treatment and the effectiveness of the dosage in treating the cancer will determine the final dosage on which the patient is maintained for the duration of the therapy.

When given intravenously, such as for breast or ovarian cancer, the initial dose is 0.4 milligram per kilogram (mg/kg) of body weight. Once the best dose for an individual patient is determined, it is given every one to four weeks.

For bladder cancer patients, an initial treatment of 60 mg of thiotepa that has been dissolved in 60 milliliters (ml) of sodium chloride is instilled directly into the bladder. If a patient has difficulty retaining this volume for two hours, the dose is reduced to 30 ml. The typical treatment cycle is once a week over a four-week period.

The dosage of thiotepa for the treatment of effusion ranges from 0.6 to 0.8 mg/kg. The dosage and duration of treatment varies with the specific site of the condition, and can be as frequent as one to two times per week.

Because myelosuppression is a common reaction to this drug treatment, white blood cell and platelet counts are carefully monitored, usually weekly during the treatment and for three weeks after. This condition may limit the dose level that a patient can tolerate. If blood counts are below a certain level, treatment is either postponed or the dosage is decreased in the next treatment cycle.

Precautions

As with many chemotherapy drugs, vaccines should not be given to patients taking thiotepa, and patients should avoid contact with people who have recently taken the oral polio vaccine. Myelosuppression can increase the chance for infection and bleeding. Contact with people who have an infection should be avoided. To decrease the chance for bleeding, aspirin or aspirin-containing medicines should not be taken. High doses of thiotepa can lead to severe cases of myelosuppression and may increase a patient's chance for a later occurrence of leukemia.

Side effects

Myelosuppression, usually neutropenia (decrease of the infection-fighting white cells) or thrombocytopenia (decrease of the platelets responsible for blood clotting), is common and usually occurs one to three weeks after each treatment, but may last throughout the therapy. Nausea and vomiting are uncommon and are most likely to occur six to twelve hours after the drug is given. Dizziness or a mild headache can occur within the first few hours after a treatment. Anorexia , stomatitis , diarrhea , infertility, fever , and alopecia are uncommon. Severe myelosuppression, stomatitis, memory change , and problems with thinking or speaking may result from high dose treatments. Side effects for bladder cancer treatment can include pain when urinating, blood in the urine, or inflammation of the bladder.

Coping with side effects may require making some life-style changes or in some cases, such as nausea, taking medication. Treatment options for side effects should be discussed with a doctor.

Interactions

Thiotepa combined with nitrogen mustard chemotherapy drugs such as cyclophosphamide or combined with radiation therapy does not improve the response to this treatment and can intensify some side effects, such as myelosuppression and infertility.

Monica McGee, M.S.

KEY TERMS

DNA (Deoxyribonucleic acid)

—The genetic material found in each cell in the body that plays an important role in controlling many of the cell's 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.

Effusion

—The collection of fluid in a body cavity or tissue due to the rupture of a blood or other body vessel, resulting from type of trauma, cancer, or other condition.

Lymph system

—This system is involved in preventing bacteria and other infection-causing particles from entering into the bloodstream. It is made up of small organs called lymph nodes, which make and store infection-fighting cells, and thin tubes, or vessels, that branch into all parts of the body.