Part 6

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42. What is the blood-brain barrier? How does it determine which drugs are used in brain tumor treatment?

The tiny blood vessels or capillaries of the brain that deliver oxygen and nutrients to the cells differ from the capillaries of other organs. The walls of the capillaries of most of the body are porous, so that molecules move freely from the blood stream into the tissues. The walls of the capillaries of the brain, on the other hand, are more tightly joined together. This tight seam or “junction” restricts the movement of larger molecules, including drug molecules, into the brain. The blood-brain barrier refers to the limitation imposed on drugs and other substances from crossing the capillary walls into brain tissues.

Clearly, there are many drugs that readily pass into the brain (for example, alcohol, cocaine, and all types of "recreational" drugs!), but other drugs have physical characteristics that prevent their passage through the capillaries. Some brain tumors have more "leaky" capillaries, and therefore do not have an intact blood-brain barrier. These tumors tend to show an area of bright contrast enhancement on MRI when intravenous gadolinium has been used (see Question 16).

Some chemotherapy drugs, including carmustine (BCNU), lomustine (CCNU), temozolomide (Temodar), and procarbazine (Matulane), have the ability to cross the intact blood-brain barrier. The drugs cisplatin and carboplatin do not cross the intact blood-brain barrier well, but they may be effective in malignant tumors, which have capillaries that are more porous.

The significance of the blood-brain barrier in determining the success of chemotherapy in brain tumors has been debated for many years. The presence of "leaky" capillaries within the tumor may allow the chemotherapy drug to kill more of the surrounding tumor cells. It is possible to open the blood-brain barrier temporarily with other drugs. This process, called blood-brain barrier disruption, has been developed in some research centers as a way to achieve higher concentrations of chemotherapy to the tumor and to the surrounding brain tissues, which may contain scattered tumor cells. This has been particularly useful in treating primary CNS lymphoma, which is a very chemotherapy-sensitive tumor.

Unfortunately, the blood-brain barrier does not prevent systemic cancers, such as breast cancer and lung cancer, from spreading into the brain and spinal fluid. It may, however, limit the penetration of chemotherapy drugs into the brain. For example, a lung cancer patient taking chemotherapy may have shrinkage of his lung cancer at the same time that metastases in the brain are continuing to grow.

43. What is chemotherapy? What are the most common drugs used to treat brain tumors? What are their side effects?

Chemotherapy refers to the medication used to treat cancer that has direct effects on the growth and proliferation of cancer cells. There are hundreds of chemotherapy drugs, and they are divided into different classes depending on how they affect the cell. Most chemotherapy drugs interfere with the reproductive cycle of cancer cells by affecting their DNA, but some block other steps in cell division. Unfortunately, the effects of chemotherapy on some of the body's normal cells, particularly the rapidly dividing cells of the bone marrow, can cause considerable toxicity. Because the bone marrow produces red blood cells, white blood cells, and platelets, chemotherapy can kill these cells, sometimes placing the patient at risk for infection or bleeding.

Chemotherapy is usually given in cycles. Each cycle consists of the day or days in which chemotherapy is given and the time it takes for bone marrow to recover or other toxicity to resolve. The cycle length varies according to the drug or combination of drugs; it may be as short as 3 weeks or as long as 8 weeks.

It is difficult to list all of the drugs that have been used in the treatment of primary and metastatic tumors. However, some drugs have been developed specifically for the treatment of primary brain tumors. Others have shown effectiveness in clinical trials; some of these drugs are already approved by the Food and Drug Administration (FDA) to treat other conditions. These drugs may be considered off-label for use in the treatment of brain tumors (see question 60). Some drugs are best known by their generic name and others by their trade name; the names used most commonly, in bold type, will be used for simplicity.

The drugs BCNU (carmustine) and CCNU (lomustine) are some of the oldest drugs used to treat astrocytomas, oligodendrogliomas, and many other types of brain tumors. BCNU is an intravenous drug; and its chemically related cousin, CCNU, is an oral drug. BCNU and CCNU have good penetration across the blood-brain barrier, but they may affect blood cell counts for several weeks; therefore, these drugs are commonly given in cycles 6 to 8 weeks apart. In addition to their effects on blood cell counts, these drugs can cause lung scarring (pulmonary fibrosis), a condition that may cause shortness of breath. BCNU and CCNU have been used in combination with other chemotherapy drugs. For example, CCNU is commonly used in combination with procarbazine and vincristine in a drug regimen known as PCV.

BCNU has been incorporated into a wafer, which is designed to dissolve in the brain when placed into the surgical cavity following tumor resection. The Gliadel wafer does not affect blood cell counts or cause lung toxicity, but it may not be used in patients whose tumors cannot be resected. When using Gliadel, the neurosurgeon must take precautions to make sure spinal fluid containing BCNU does not contaminate the surgical wound. Currently, Gliadel is approved to treat glioblastoma multiforme, although off-label use of the wafer has included patients with other resectable primary or metastatic tumors.

Temozolomide (Temodar) is an oral drug developed in Europe that was approved for treatment of recurrent anaplastic astrocytoma in the United States in 1999. Since that time, many other tumor types have been studied in clinical trials with Temodar. Some clinical trials have explored the use of Temodar in combination with other drugs and with radiation therapy. Many different administration schedules have also been used, but the most common schedule used in the United States recommends that Temodar is taken daily, at bedtime, for 5 days, every 4 weeks. Most patients tolerate Temodar well without experiencing significant effects on blood counts. Temodar has not been shown to cause lung damage. It may cause nausea and constipation, but both can usually be controlled with other medications.

Procarbazine (Matulane) is an oral chemotherapy drug that may be used alone or in combination with other chemotherapy drugs. This drug, however, interacts with other drugs, including antihistamines, narcotics, some nausea medications, and alcohol. Procarbazine can also cause high blood pressure when used in combination with foods high in tyramine, such as brewer's yeast, chicken livers, bananas, and aged cheese. A study comparing Temodar and procarbazine in recurrent glioblastoma found that Temodar causes less toxicity and appears to be more effective than procarbazine, although procarbazine is still widely used in combination therapy.

Methotrexate has been used primarily to treat CNS lymphoma, often given in high doses and followed with administration of leucovorin, a drug that acts as an antidote for methotrexate toxicity in normal cells. High doses are necessary to penetrate into spinal fluid and treat leptomeningeal cancer cells.

Carboplatin (Paraplatin) and cisplatin are commonly used to treat lung cancer, ovarian cancer, and other malignancies. They have been used intravenously and intra-arterially in primary brain tumors. Both are commonly given with other drugs. Cisplatin may cause kidney damage, peripheral neuropathy (numbness and tingling, particularly in the lower extremities) and severe nausea.

Cyclophosphamide (Cytoxan) is an intravenous drug that has been used for pediatric and adult brain tumors such as medulloblastoma. It causes low blood cell counts and nausea.

CPT-11 (Camptosar, also called irinotecan) is an intravenous drug that was originally approved to treat colon cancer. Clinical trials have shown that CPT-11 to be effective in treating malignant glioma. Several different doses and schedules have been used.

Etoposide (VP-16) has been used orally and intravenously to treat many different types of cancer. It has been used in combination with other drugs to treat medulloblastoma, germinoma, and primitive neuroectodermal tumors. It has also been used to treat metastatic small cell lung cancer.

Vincristine (Oncovin) is rarely used as a single drug in the treatment of cancer, but it is often used in combination with other drugs because it does not affect blood cell counts. However, vincristine may cause numbness, weakness, constipation, impotence, and other significant side effects. This drug is given intravenously.

Many other chemotherapy drugs have been used alone or in combination with other drugs to treat primary and metastatic brain tumors. Your oncologist or oncology nurse will give you references and information regarding the possible side effects of the drugs recommended to you before you start treatment.

44. Why are my blood cell counts affected by chemotherapy? Are low blood cell counts dangerous? What can I do to keep my blood cell counts high during chemotherapy?

Because many chemotherapy drugs interfere with cell division, the rapidly dividing cells of the bone marrow— the white cells, red cells, and platelets — are the "innocent bystanders" of the toxic effects of chemotherapy. Fortunately, blood cell counts usually recover rapidly, often within days, but some drugs have longer effects on the blood cell counts. Your doctor or nurse will explain to you which of your blood cell counts may be affected by your chemotherapy and what you should expect while your blood cell counts may be low. If your blood cell counts remain lower than expected, it may become necessary for your doctor to reduce the dosage of your chemotherapy.

White blood cells (neutrophils, lymphocytes, and monocytes) protect your body against infection. Neutrophils, also called segmented neurophils or polymorphonuclear leukocytes, are the first line of defense against bacterial infections and fungal infections. These cells often multiply rapidly during the early stages of an infection. For example, a high white blood cell count may signal a serious infection such as pneumonia. However, if the patient is undergoing chemotherapy, the white blood cell count may be lower than usual. Particularly when the neutrophil count is very low (a condition called neutropenia), the patient is at more risk for severe infection. It is important to notify your doctor if you develop a fever, cough, or other symptoms of infection when your white cell count may be low. A number of different drugs, including sargramostim (Leukine), filgrastim (Neupogen), and pegfilgrastim (Neulasta), may be administered by injection to stimulate recovery of your neutrophil count to normal. In some situations, your doctor may need to hospitalize you to treat fever or infection while your white blood cell count is low.

The red blood cell count may also be affected by chemotherapy. A low red blood cell count (anemia) may result from a number of other causes, including iron deficiency. For this reason, you should be careful to include iron-rich foods in your diet while you are on chemotherapy. Anemia can cause fatigue and shortness of breath. In severe cases of anemia, it may be necessary to have a transfusion of red blood cells. Epoetin alfa (Procrit), an injectable red blood cell growth factor, may be recommended by your oncologist if your red blood cell count falls during chemotherapy.

Platelets are important in normal clotting, and a very low platelet count (thrombocytopenia) may be associated with severe bleeding. If necessary, a low platelet count can be treated with transfusion. Oprevelkin (Neumega) is an injectable drug that is used to stimulate the recovery of platelets. It is administered for several days following chemotherapy, when thrombocytopenia is anticipated.

45. I've heard terrible things about chemotherapy and the nausea and vomiting associated with it. Will I be very ill while I'm on chemotherapy?

Fortunately, many of the side effects of chemotherapy that were distressing to patients in the past are now avoided because of widespread use of antiemetic (anti-nausea) medications that were developed specifically for chemotherapy. Medications such as ondansetron (Zofran), granisetron (Kytril), and dolesetron (Anzemet) can be given intravenously or orally before chemotherapy. These drugs, unlike some of the older medications, do not cause sedation, making it safer for patients to receive chemotherapy in the outpatient setting. Many of the chemotherapy drugs used to treat brain tumors, such as BCNU, CCNU, and Temodar, may cause nausea. Oncologists recommend that patients receive antiemetic medication before taking the chemotherapy rather than waiting to see if nausea will develop. It is particularly important to prevent vomiting when taking an oral chemotherapy drug, because it cannot be "doubled up" if a dose is missed.

M.L.'s comment:

I think the fear of nausea and vomiting is the most common concern with chemotherapy. It certainly was for me! I rarely experienced any sickness while I was on chemotherapy and I could hardly believe it. I took temozolomide for 23 months and only had severe nausea on the first night that I took it. I think I probably was so nervous about whether or not I would get sick that I probably brought the nausea and vomiting on myself. I'll never really know whether it was the drug or my nerves that made me sick, but I do know that I took the anti-nausea medication every single time that I took my temozolomide and it helped.

The side effect that I DID have was just a general feeling of being tired, but not so tired that I couldn't go to work. There were days that I would go home early or go in late. For the first couple of days that I was on chemotherapy, I was fine. I didn't feel tired at all. However, as the week went on and more chemotherapy was in my body, I started to become more tired. I remember wanting to sleep in later than usual, and I would fall asleep earlier in the evening than usual. This wasn't really a bad thing. I just felt like it was the reality of being on chemo, and hey, it was a lot better than the feeling nauseous.

Another side effect that I felt was loss of appetite. For me, that was a good thing because I had gained so much weight while I was on steroids that I wanted to lose some weight. In talking with others who were on temozolomide, I found that the loss of appetite affects everyone differently. There were some people who said they didn't have much of an appetite for anything. Others, like me, only had a slight loss of appetite. The good news was that my normal appetite came back shortly after I finished each round of chemotherapy.

One other side effect that occurred while I was taking temozolomide was extreme constipation. If you've ever been really constipated you know that it isn't something that you want to experience very often. I found that I didn't experience the constipation if I took a powdered laxative mixed in with orange juice once a day for every day that I was on chemotherapy. Most of the time, I would extend taking the laxative a few more days until I felt like the chemotherapy had gone through my system and my appetite was back to normal.

All in all, my experience with temozolomide was surprisingly positive. I didn't get sick and I didn't lose my hair. Yes, I was a little fatigued and my appetite was down, but this only lasted for about a 5 to 7 days. Once I figured out how to address the constipation that wasn't even an issue any more. In short, I'll take the fatigue, loss of appetite, and the constipation over NOT getting sick or losing my hair any day of the week!

The decision of when to take chemotherapy is only one part of the problem. The other issues are what chemotherapy to take, how long to take it, and why chemotherapy should be taken for the particular type of tumor you have.

As with other issues regarding treatment, if you are considering participation in a clinical trial, you must make certain that you will keep your eligibility for the trial. Some clinical trials do not allow patients who have had chemotherapy to participate. Others will not allow patients to participate after radiation therapy until their tumor grows enough to become apparent on MRI. If participating in a specific clinical trial is important to you, be sure to contact the center offering the trial before you begin another treatment.

In general, chemotherapy is offered to patients who have a high likelihood of recurrence, either because the tumor cannot be cured by surgery or radiation therapy alone, or because a previous randomized trial indicated that the addition of chemotherapy prolonged survival. For low grade glioma, for example, a long duration of survival is common following treatment with radiation therapy, but only a few trials have been completed using chemotherapy immediately after radiation therapy. In one of these trials, CCNU offered no improvement in survival for patients with low-grade gliomas over radiation therapy alone. On the other hand, in patients with high-grade gliomas, the addition of BCNU or CCNU to radiation therapy appeared to improve survival. The initial studies of Temodar were conducted in patients who had had regrowth of tumor weeks or months after radiation therapy. More recent studies of using Temodar immediately following radiation therapy in patients with high-grade gliomas have also suggested an improvement in survival. Other studies have combined radiation therapy and Temodar in newly diagnosed patients. It is not yet clear which approach results in the best overall survival.

Theoretically, the optimal time to begin chemotherapy for any type of cancer when there are only a few tumor cells present. If surgery and radiation therapy have eliminated the majority of tumor cells, the few that remain may be treated with chemotherapy successfully. However, this scenario is only true when the chemotherapy chosen is known to be effective against the tumor cells. Because of the differences in their sensitivity to chemotherapy, it is anticipated that some cells will remain after treatment with a given chemotherapy agent. This is why multiple drugs have been used either simultaneously or sequentially to treat residual tumor.

For most brain tumors, the optimal duration of chemotherapy treatment that follows surgery and radiation therapy is not known. In the past, when drugs such as CCNU and BCNU were the mainstay of treatment, few patients could tolerate several months of therapy because of the development of toxicity to the bone marrow and lungs. Newer drugs such as Temodar are not as toxic, and many patients can tolerate treatment for a year or longer. However, if there is no evidence of residual tumor on MRI after several months of treatment, it is still not clear if patients should continue chemotherapy or continue follow-up without active treatment (see Question 52).

Remember that there is not just one right answer to questions regarding treatment. A number of different treatment approaches have been developed over the past ten years, and recommendations continue to evolve from the results of clinical trials. If you desire aggressive treatment because of the possibility of residual tumor, you should communicate this to your oncologist.

47. Why are some drugs given orally, through a vein, or through an artery, whereas other drugs are delivered into the spinal fluid or into the tumor cavity?

All of the drugs commonly used in the treatment of cancer have been studied for several years in research animals and in clinical trials. During those studies, some drugs were noted to be easily absorbed through the gastrointestinal tract when taken orally, a characteristic called bioavailability. However, some drugs are not absorbed or lose their effectiveness when administered orally. These drugs have not been manufactured in an oral form and are only available as an injectable (usually intravenous) preparation. Temodar is an oral drug with good bioavailability; CPT-11 has poor bioavailability and is always given intravenously.

Relatively few drugs have been studied by directly injecting them into an artery that supplies the tumor (intra-arterial administration). Also, only a few drugs have been proven safe to inject directly into spinal fluid (intrathecal administration). In general, research centers that specialize in drug development use animal models to determine the safety and effectiveness of drugs to use by these special routes. The chemotherapy wafer Gliadel, which contains the drug BCNU, is currently the only chemotherapy approved for administration into the tumor cavity (intracavitary administration). Methotrexate is one of the few drugs that can be given intravenously, intra-arterially, intrathecally, and orally.

Remission (from the Latin word remissio, to send back) means that the symptoms of a disease and the objective evidence of the disease have partially or completely resolved. A partial remission, or PR, means that some evidence of the tumor remains. In a clinical trial, at least a 50% reduction in the original size of the tumor must occur before a patient is considered a PR. The complete resolution of all signs and symptoms of disease is a complete remission, or CR. Because of the post-treatment abnormalities that may persist for several months on MRI, it can be difficult to define when a brain tumor patient achieves CR.

However, having a normal MRI scan for months or years does not necessarily mean that a patient is cured. Most people would define cure as the permanent eradication of disease. It would be impossible to verify over a period as short as 12 months that the disease is permanently eradicated. In the absence of effective treatment, microscopic disease may eventually grow back into visible tumor.

Although most patients want to know what their chances are for cure, the answer is never 100%, and it is never 0%. The chance of achieving remission, however, may be quite high. The next question typically asked is: "How long will the remission last?" Because of the variation in growth rates among different types of brain tumors, this can also vary widely. For example, primary CNS lymphoma is a malignant tumor that may involve the brain and spinal fluid. If a patient completes treatment and the MRI of the brain shows no evidence of disease, but the patient still has malignant cells in the spinal fluid, the patient's "response" to treatment would be considered a PR. A patient is considered a CR only when all evidence of disease has resolved with treatment. In some studies, the proportion of CNS lymphoma patients achieving a complete remission may exceed 50%. Some of those patients may be cured. However, because of the known risk of relapse, these patients are followed regularly for any recurrence of disease. In fact, a complete remission may last only a matter of weeks after discontinuing treatment.

It is important to understand that in using the word "remission," your doctor is not trying to avoid the word "cure." Your doctor is merely trying to describe as accurately as possible the presence or absence of disease.

For patients who have cancer cells in the spinal fluid, often called leptomeningeal spread, small doses of chemotherapy can be injected into the spinal fluid to circulate in the ventricles and over and around the spinal cord and spinal nerves. Although some patients receive chemotherapy injections with a spinal tap or lumbar puncture, this may be impractical or technically difficult for patients who require treatment for several months.

An Ommaya reservoir is a hollow, slightly dome-shaped, silicone device that is attached to a catheter, surgically implanted by a neurosurgeon in the operating room The catheter is threaded though a small hole in the skull, into the non-dominant cerebral hemisphere, often the right frontal lobe (Fig. 11). The hollow reservoir is slipped between the skin of the scalp and the skull and sutured in place. The slightly rounded surface of the reservoir allows your doctor to locate its placement and the surface of the skin is cleansed with antibacterial solution. A butterfly needle is inserted through the skin into the dome to "access" the reservoir. Spinal fluid is removed by slowly aspirating with a syringe, and chemotherapy is then administered by injecting into the reservoir and catheter. Most patients have no discomfort when chemotherapy is administered through the Ommaya reservoir, and the procedure can be easily performed within minutes on an outpatient basis.

Strict adherence to sterile technique is essential when the reservoir is accessed because introduction of infection into the spinal fluid can be life-threatening. Fortunately, once the skin at the insertion site of the reservoir heals, no special precautions are required on the part of the patient.

Patients who have an Ommaya reservoir for chemotherapy may require lifelong re-evaluation of the spinal fluid to detect evidence of recurrence. For this reason, the Ommaya reservoir is considered a permanent device. It is not removed at the end of treatment.

Table 4 lists drugs that have been used for intrathecal therapy. Methotrexate is by far the most common drug used in intrathecal therapy. DepoCyt, which was approved a few years ago, is specifically formulated to persist over time, so that it requires less frequent injections. Newer drugs, such as topotecan, are still being studied in clinical trials to determine which tumors respond best. Your oncologist will provide further information about the drug and potential side effects before you begin treatment.

Drugs Used in Intrathecal Therapy	Types of Cancer Treated
Methotrexate	Breast cancer, lymphoma, leukemia
Cytarabine (Ara-C)	Lymphoma, leukemia
DepoCyt (liposomal encapsulated cytarabine)	Leukemia, lymphoma
Thiotepa	Lymphoma, leukemia, breast cancer
Etopophos	Lymphoma, lung cancer, germinoma, glial tumors
Topotecan	Lymphoma, small cell lung cancer, glial tumors
Dacarbazine	melanoma

50. Why should I have a different type of chemotherapy if the first type didn't work?

Chemotherapy drugs that belong to different classes may have different success rates. In general, it is difficult — if not impossible — to predict at diagnosis which drug is best for a given patient. Recently, Precision Therapeutics developed testing procedures to determine the most effective drugs against a patient’s tumor. The assay requires that a portion of the live tumor removed during surgery be submitted for analysis. Although the assay takes several days, it may be possible to identify certain drugs that are more effective against the tumor (Fig.12). However, there is still a chance that the patient will develop intolerable side effects to the drug. For this reason, pre-treatment predictive testing is not always helpful.

In some instances, a drug that is chemically distinct from the first drug used may be more effective. For example, it is known that brain tumor cells are sometimes resistant to the chemotherapy drug BCNU. Therefore, tumor cells that are resistant to BCNU may also be resistant to CCNU because the drugs are closely related. The drug CPT-11, however, is from a different class of drugs. It kills tumor cells in a different way than BCNU or CCNU, so tumor cells may not be resistant to this drug.

51. What are the other drugs besides chemotherapy that could be used to treat my tumor?

There are a number of different drugs that have been used to treat malignant brain tumors, some alone and some in combination with chemotherapy. The majority of clinical trials to determine the effectiveness of these drugs have been conducted in patients with malignant glioma, so less is known about their usefulness in the treatment of other types of brain tumors.

Accutane (13-cis-retinoic acid) is an oral drug that has been approved for the treatment of cystic acne. It is known that some malignant gliomas have an epidermal growth factor receptor (EGFR) which, when chemically blocked, prevents cell division. Accutane appears to block the EGFR receptor. Clinical trials have shown that some patients are long-term survivors when given high-dose Accutane therapy. Accutane has also been used in combination with Temodar, improving survival over Temodar alone. Although Accutane has shown to improve survival, it does have side effects, including dry skin and lips, headache, and nausea. It can also cause birth defects. An assay to detect the presence of EGFR on tumor cells is commercially available. Other drugs known to inhibit cell division through EGFR are also in development.

Thalidomide (Thalomid), another oral drug, is believed to inhibit growth of tumor cells by interfering with the tumor's ability to grow new blood vessels (anti-angiogenesis). Thalidomide was developed as a sedative in Europe, but was associated with devastating birth defects. It did not receive FDA approval until it was shown to be effective in treating leprosy. Thalidomide is effective in the treatment of a blood disorder, multiple myeloma, and has also been used in clinical trials for patients with malignant glioma. Used alone, it seems to slow the growth of tumors, although some patients experience tumor regression. Thalidomide has been used in combination with Temodar, CPT-11, and carboplatin. Its major side effects, sedation and constipation, are usually manageable. Both male and female patients are required to practice effective contraception while taking thalidomide.

Other drugs commercially available that may inhibit angiogenesis include the new cyclooxygenase-2 inhibitors, Vioxx and Celebrex, which are typically used to treat arthritis. In addition to treating arthritis, these drugs have shown to inhibit tumor growth in animal models. Both drugs have been used in the treatment of cancer, alone and in combination with chemotherapy. Side effects include nausea, headache, and stomach ulcers.

Tamoxifen (Nolvadex) has been used for several years in the treatment of breast cancer. When administered in higher doses, this drug has shown to be effective in the treatment of malignant glioma. It is believed that at higher doses tamoxifen inhibits a cell-signaling enzyme called protein kinase C, which prevents glioma cell division. Doses of tamoxifen used for treating brain tumor patients are 10 to 12 times higher than those commonly used for treating breast cancer. Higher doses of tamoxifen may be associated with deep vein thrombosis, the formation of blood clots in the extremities (see Question 69). It may also cause nausea, hot flashes, and weight gain. A recent study suggested that patients on high-dose tamoxifen had an improvement in survival when first treated with medication to reduce thyroid hormone production.

A number of other non-chemotherapy drugs are in clinical trials. Because many are considerably less toxic than chemotherapy, new combinations of non-chemotherapy drugs and standard chemotherapy regimens appear promising.

52. How long should I stay on treatment?

The duration of treatment depends on many factors, but ultimately, it depends on your response to treatment and the toxicity that you experience while on treatment. Patients on clinical trials may have a specific duration of therapy planned as part of the trial or may continue therapy as long as their tumor appears to be responding. Some oncologists stop treatment after the tumor has been in remission for at least two months, but it is often difficult to determine whether there is active tumor remaining.

Nitrosoureas such as BCNU and CCNU have cumulative toxicity, sometimes causing prolonged periods of low blood counts as treatment continues. Both drugs may also be associated with lung scarring (pulmonary fibrosis), which may be irreversible. These drugs are rarely given for a year or more for this reason. However, drugs such as Temodar, Procarbazine, and CPT-11 have been given for prolonged periods without significant cumulative toxicity. Preliminary studies indicate that patients with malignant glioma who continue Temodar for longer than one year have an improvement in overall survival. Also, drugs such as Accutane, thalidomide, and tamoxifen may be taken without significant long-term toxicity, but no one knows the optimal duration of therapy.

53. Are all types of chemotherapy for brain tumors covered by insurance?

Private insurance, Medicare, and Medicaid may pay for some types of chemotherapy but not for others. For example, intravenous drugs such as BCNU may be covered by all three providers. Temodar is covered for primary brain tumors by most private insurers, and Medicare covers some — but not all — of the cost. However, off-label use of drugs may not be covered by Medicare or Medicaid. Even some private insurers may not cover a drug that is considered "experimental." Check with your doctor or with your insurance company if you are unsure about whether your chemotherapy is covered.

54. Does oral chemotherapy have fewer side effects than intravenous chemotherapy?

The side effects of chemotherapy vary from person to person, and it is not always possible to predict their severity. Some oral drugs have similar side effects to intravenous drugs. For example, CCNU (oral) and BCNU (intravenous) both cause nausea and low blood cell counts. For patients who have had severe nausea and vomiting, BCNU may be a more appropriate choice because the drug is given in a vein. Patients who have vomiting after taking oral chemotherapy such as CCNU may thus receive less than the full dose intended.

Sometimes it may be difficult to find a suitable vein for the administration of chemotherapy. One problem that is avoided with oral chemotherapy is the insertion of an intravenous catheter.

Your oncologist will discuss with you the expected side effects of chemotherapy as well as how to manage the side effects if they occur.

55. Is it possible to get pregnant while on chemotherapy?

Yes -- but it is very important to avoid pregnancy during chemotherapy and radiation therapy. Exposure to radiation therapy and chemotherapy, particularly early in pregnancy, is associated with a high risk to the fetus. Even later in pregnancy, chemotherapy may cause low birth weight and low blood counts in the unborn child.

Reliable contraception is recommended for all women of childbearing potential while undergoing treatment for a brain tumor. Chemotherapy can induce temporary or permanent infertility, and many female patients experience a change in their menstrual periods while receiving chemotherapy. Some patients experience premature menopause (their periods never return) and some resume their periods and normal fertility following chemotherapy.

A waiting period of several months following treatment with chemotherapy is also recommended for women who are considering pregnancy. This allows for recovery from the side effects of therapy. For women whose menstrual periods return to normal and are able to conceive, there does not appear to be an increased risk of birth defects.

56. If I return to work at my desk job while I'm on chemotherapy, will I have to take any special precautions?

Returning to work is a positive experience for many people who may have been away for several weeks after surgery or other treatment. However, most patients find that they are more fatigued than expected and may require more frequent breaks or a shorter work schedule. Even if you have a desk job, it is common to feel exhausted at the end of the day.

In addition to adequate rest, getting regular exercise and good nutrition are important for maintaining a sense of well-being while on chemotherapy. Patients who have nausea from their chemotherapy may be able to arrange their work schedules to allow more time off after chemotherapy. They may also be able to take non-sedating antiemetic medication.

Some patients on chemotherapy have low blood counts and are at risk for infection. Working closely with co-workers who may be ill or in rooms with poor ventilation may increase the risk of infection. Antibacterial soaps or hand wipes may help limit the transmission of infection in the workplace.

57. Will I lose my hair while on chemotherapy?

Although most people assume that hair loss is a universal side effect of chemotherapy, alopecia is actually uncommon with many of the drugs used to treat brain tumors. BCNU, CCNU, procarbazine, and Temodar usually do not cause hair loss. Drugs that may cause partial or complete hair loss include vincristine, CPT-11, Cytoxan, and etoposide.

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Copyright © 2004 dfw-neuronetwork
Last modified: Saturday June 18, 2005