thiotepa

n.
A crystalline compound, C₆H₁₂N₃PS, a sulfur-containing analogue of tepa, used to treat certain malignant tumors.

Key Terms: DNA, Effusion, Lymph system.

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.

According to reports, Thiotepa conditioning regimen in patients with advanced hematologic neoplasms is associated with renal and hepatic toxicity. Relapse of hematologic malignancies after allogeneic stem cell transplantation remains a common problem, in particular for patients who have advanced disease at the time of transplantation. Researchers concluded that this regimen requires modification to reduce toxicity.

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.

Chemical formula:

Español:
• Tiotepa, Solución para inyección

Thiotepa Solution for injection

What is this medicine?

THIOTEPA is a chemotherapy drug. It slows the growth of cancer cells. This medicine is used to treat many types of cancer like breast cancer, ovarian cancer, bladder cancer, and lymphoma.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• infection (especially virus infection such as chickenpox or herpes)
• kidney disease
• liver disease
• low blood counts like low platelets, red blood cells, white blood cells
• recent radiation therapy
• an unusual or allergic reaction to thiotepa, other chemotherapy, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This drug is given as an infusion into a vein. It may also be given into the bladder or into a body cavity. It is administered in a hospital or clinic by a specially trained health care professional.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

• medicines to increase blood counts like filgrastim, pegfilgrastim, sargramostim
• other chemotherapy drugs
• vaccines

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor for checks on your progress. This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

In some cases, you may be given additional medicines to help with side effects. Follow all directions for their use.

Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.

This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.

Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. Men should inform their doctor if they wish to father a child. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• low blood counts - this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
• signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
• signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
• signs of decreased red blood cells - unusually weak or tired, fainting spells, lightheadedness
• breathing problems
• changes in vision
• irritation at site where injected
• nausea, vomiting
• pain at site where injected

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
• hair loss
• headache
• loss of appetite
• missed menstrual periods
• stomach upset

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Triethylenethiophosphoramide; a cytotoxic alkylating agent used as an antineoplastic agent.

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