Chemotherapy for gestational trophoblastic disease

Chemotherapy (chemo) uses anti-cancer drugs that are injected into a vein or given by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers that have spread to distant organs (metastasized). GTD is one of the few cancers that can almost always be cured by chemo no matter how advanced it is. The best indicator of which drug to use is the prognostic score.

The drugs that can be used to treat GTD include:

• Methotrexate (with or without leucovorin)
• Actinomycin-D (dactinomycin)
• Cyclophosphamide (Cytoxan^®)
• Chlorambucil
• Vincristine (Oncovin^®)
• Etoposide (VP-16)
• Cisplatin
• Ifosfamide (Ifex^®)
• Bleomycin
• Fluorouracil (5-FU)
• Paclitaxel (Taxol^®)

To reduce the risk of side effects, doctors try to give the fewest drugs at the lowest doses that will still be effective. As a general rule, women who need to get chemo and fall into the low-risk group (see the section, "How is gestational trophoblastic disease staged?") are given a single chemo drug. Women who fall in the high-risk group usually receive combinations of drugs, often at higher doses.

Single drug treatment

Methotrexate: Chemotherapy with methotrexate alone can be used in most women with low-risk disease. The methotrexate can be given as an injection into a vein or a muscle every day for 5 days. This can be repeated again after a rest period based on the HCG level. Another way to give methotrexate is to give a larger dose once a week. Again, the treatment is continued as long as needed, based on the HCG level.

Another option is to give methotrexate along with folinic acid (also called leucovorin). Leucovorin is not a chemo drug, but instead is a type of vitamin related to folic acid that reduces the toxic effects of methotrexate. In this course of treatment, methotrexate is given on days 1, 3, 5, and 7, and leucovorin is given on days 2, 4, 6, and 8. Each cycle has 8 days of drug treatment, followed by a rest period. This method has more treatment days, so it may be less convenient. In all cases, methotrexate is given in cycles that are repeated until blood levels of HCG remain normal for a few weeks. Vitamins such as folic acid can make methotrexate less effective and so should not be taken with this drug unless directed by your doctor.

Actinomycin-D: Another option is to give actinomycin-D instead of methotrexate. This drug may be especially useful in patients with liver problems, because it is less toxic to the liver than is methotrexate. Actinomycin-D is given in a vein (intravenously, or IV) every day for 5 days, followed by several days without treatment. It is also given as a larger single dose once every 2 weeks. This schedule seems to have fewer side effects while still working well. Either way, the cycles are repeated until HCG levels have stayed in the normal range for several weeks.

Combinations of drugs

Women with higher-risk disease will receive combinations of drugs such as methotrexate, actinomycin-D, and cyclophosphamide. Other drugs such as etoposide, vincristine, and cisplatin may also be used.

Some of the more commonly used combinations include:

• MAC: methotrexate/leucovorin, actinomycin-D, and cyclophosphamide or chlorambucil
• EMA-CO: etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by cyclophosphamide and vincristine (Oncovin)
• EMA-EP: etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by etoposide and cisplatin ("platinum")
• VBP: vinblastine, bleomycin, and cisplatin
• BEP: bleomycin, etoposide, cisplatin

Possible side effects

Chemo drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to some side effects.

The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. Common side effects of chemotherapy drugs include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Low blood counts

Because chemotherapy can damage the blood-producing cells of the bone marrow, the blood cell counts might become low. This can result in:

• Increased chance of infections (from too few low white blood cells)
• Easy bruising or bleeding (from too few blood platelets)
• Fatigue (from too few red blood cells)

Most of these side effects are short-term and tend to go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Do not hesitate to discuss any questions about side effects with the cancer care team.

Along with the effects listed above, some side effects are specific to certain medicines:

Common side effects of methotrexate are diarrhea and sores in the mouth. This drug can also cause mild liver damage which is seen as changes in certain blood tests (liver enzymes). Some women have inflammation of the eye (conjunctivitis), pain in the chest or abdomen, irritation in the genital region, or skin rash. Hair loss and blood side effects do not usually occur with single-drug methotrexate therapy.

Actinomycin-D can cause fairly severe nausea and vomiting. This can be prevented by medicines given before chemo. Treatment with actinomycin-D or combination therapy is more likely to result in hair loss. Your bone marrow's ability to produce blood cells may be affected, which in turn may lower the ability of your immune system to fight infection.

Bleomycin can cause lung problems. These occur more often in patients who smoke.

Cyclophosphamide and ifosfamide can cause some nausea and hair loss. They can also cause bladder irritation and rarely cause severe lung problems.

In rare cases, etoposide treatment has been linked with the development of leukemia several years later. Cisplatin has also been linked to this, although it occurs less often than with etoposide. But doctors still consider these drugs important to use because their benefit in curing the cancer outweighs the small risk of leukemia.

Vincristine and cisplatin can damage nerves (called neuropathy). Patients may notice tingling and numbness, particularly in the hands and feet. Cisplatin can also cause hearing loss and kidney damage. These side effects may persist after treatment stops.

You should report any side effects or changes you notice while getting chemotherapy to your medical team so that they can be treated promptly. In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.