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Chemotherapy and Hormone Therapy
Chemotherapy (Anticancer Drug Therapy), Hormone Therapy and Chemoendocrine Therapy (Chemotherapy and Hormone Therapy Combination) Chemotherapy is the use of drugs to destroy cancer cells. Chemotherapy interferes with the proliferation of cancer cells by damaging DNA to stop the cellsí ability to reproduce. The medical oncologist, an internal medicine specialist, plans and administers chemotherapy or hormonal therapy and coordinates the patient's management with other members of the breast cancer team. Adjuvant chemotherapy and hormonal therapy are used in combination with primary surgical or radiation treatment. Chemotherapy is used in a number of situations depending upon the patientís pathology. It is often used when there is no evidence of metastasis but the tumor appears to be aggressive (e.g., high nuclear grade, etc.), when cancer has metastasized (spread) or when it is likely that it will recur. Axillary lymph node involvement, the microscopic characteristics of the cancer cells and the presence or absence of estrogen receptors will influence the need for chemotherapy and hormone therapy. Most chemotherapy drugs are given by injection (intravenously) in brief courses of six months or shorter. Combinations of chemotherapeutic drugs (three or more are common) have become standard for adjuvant therapy. Chemotherapy is usually administered on an outpatient basis. How Chemotherapy Works to Destroy Cancer Cells Chemotherapy interferes with the proliferation of cancer cells by damaging DNA to stop the cellsí ability to reproduce. Cancer cells are not all affected by cancer killing drugs in the same way. Combinations of chemotherapy drugs are used to produce the most effective regimen to interfere with cell growth and to destroy malignant cells. This approach is referred to as combination chemotherapy. Protocols are established to create an ongoing course of chemotherapy that will attack cancer cells and destroy them by stopping them from growing or multiplying at one or more points in their life cycle. This is why common chemotherapy regimens are administered over a period of several weeks or months.
What Causes the Side Effects of Chemotherapy? Cancer cells are characterized by rapid growth. Chemotherapy is designed to ìsearch and destroyî rapidly growing cancer cells. The majority of the bodyís normal, healthy cells do not reproduce as quickly as malignant cells, and are, therefore, not compromised by chemotherapy drugs. There are exceptions to this rule, however. The body does have normal cells that reproduce faster than others and are more susceptible to chemotherapy. The cells in the hair follicles, gastrointestinal tract, bone marrow and ovaries are examples. This results in some of the more common side effects such as hair loss, nausea, diarrhea, fatigue, immunosuppression, missed periods and the early onset of menopause. Bone marrow suppression, which results in a reduced production of red and white blood cells and platelets, is the primary reason for the intervals between cycles of chemotherapy treatment. The interval period allows the affected blood cells to reproduce and return to safe levels. The side effects of chemotherapy can become more intense with the number of drugs in the protocol and with increasingly higher levels of drug dosages.
Categories of Chemotherapy Drugs and Some of Their Side Effects Alkylating Agents -- e.g., Cytoxan (Cyclophosphamide), L-Pam (melphalan), Cisplatinum, Platinol (Cisplatin) Alkylating agents have a suppressive effect on the bone marrow. A side effect associated with Cytoxan is bladder toxicity. This can be managed by keeping the body adequately hydrated (by drinking a lot of water). Mesna is a protective agent that is effective in dealing with this side effect. Hair loss (alopecia) is a possible side effect when taking Cytoxan. Cytoxan can also stop the ovaries from functioning, resulting in the temporary or permanent onset of menopause. Antimetabolites -- e.g., Methotrexate and 5-FU (Fluorourcil) Mouth sores are a common side effect of Methotrexate. Methotrexate can cause kidney damage that can be prevented or greatly reduced when Leucovorin, (a derivative of folic acid) is administered 24 hours after Methotrexate administration. 5-FU can cause skin discoloration around the injection site (that should slowly fade), nerve damage, mouth sores and diarrhea. Antitumor Antibitics -- e.g., Adriamycin (Doxorubicin) and Mitomycin C Mouth sores, injury to the skin if there is a leakage at an injection site, hair loss (alopecia) and bone marrow suppression are the most common side effects of this class of chemotherapy drugs. Adriamycin poses the risk of damaging the heart muscle and may disturb heart rhythm for several days after administration. The risk of heart damage can be reduced by administering Adriamycin at a very slow rate along with administering a compound called ADR-529 (also referred to as ICRF-187) at the same time. Currently in clinical trials, the enclosure of Adriamycin in a liposome capsule has been shown to protect against heart damage, thereby permitting higher doses of the drug. Kidney damage is a possible side effect of Mitomycin C.
Vinca Alkaloids -- e.g., Vincristine (Oncovin), Vinblastine (Velban) and Vinorelbine (Navelbine) Vincristine and Vinblastine, both derivatives of the periwinkle plant, can cause severe skin damage if they leak at the site of injection. Nerve damage is another possible side effect most often seen in patients with pre-existing diabetes or pre-existing alcoholic associated neuropathies (neuropathy is a disease involving the cranial nerves or the autonomic or peripheral nervous systems), neurologic diseases and in older patients. Vinblastine suppresses the bone marrow. Vinorelbine (Navelbine), currently in clinical trials, was developed to be as effective as the other vinca alkaloids previously mentioned and is substantially less toxic. Nausea and Vomiting and Drugs to Help -- Antiemetic (Antinausea) Medications Nausea and vomiting (emesis) occur when certain drugs stimulate an area of the brain called the chemoreceptor trigger zone. Chemotherapy induced nausea and vomiting can be well managed by giving patients antiemetic medications (such as Compazine, Kytril or Zofran) to reduce or prevent these side effects while undergoing adjuvant therapy. Antiemetics work by preventing nausea and vomiting signals from traveling to the brain. Antiemetics are often administered in combinations and can be given to patients intravenously, in pill or suppository form. Antinausea medications have side effects of their own, including fatigue and sleepiness. Zofran (Ondansetron), which can be administered intravenously or orally, has proven successful in relieving nausea in up to 85% of the patients taking it and is reported to have fewer side effects than some of the other antiemetics. Ativan, an antianxiety drug, is also used to reduce the side effects of chemotherapy. Preventing Infection and Delays in Therapy or Dose-Reducing -- The Use of Colony Stimulating Factor (CSF) Drugs As mentioned earlier, chemotherapy drugs are used to help destroy rapidly growing cancer cells. In the process, other rapidly growing normal cells may also be destroyed. The destruction of normal cells by chemotherapy drugs can include infection-fighting white blood cells called neutrophils. Neutrophils are produced in the bone marrow inside our bones and are an important part of the bodyís defense against invading bacteria and infection. When the number of neutrophils in the blood falls too low, patients are at risk for developing a serious infection. This condition is called neutropenia. Laboratory tests to monitor a chemotherapy patientís white blood cell count are performed on a routine basis, and, if the counts fall too low, treatment may have to be delayed or the patientís doctor may opt to administer a reduced dose of chemotherapy. To avoid delaying a cycle of chemotherapy or dose-reducing, medication can be administered to speed up the recovery of neutrophils. Colony stimulating factors (CSFís) are substances naturally produced by the body. CSFís stimulate the growth of various types of cells found in the blood and in the immune system. Granulocyte-Colony Stimulating Factor (G-CSF) is one type of CSF. The drug Neupogen (Filgrastim) is a form of G-CSF that is used to speed the recovery and increase the production of infection-fighting neutrophils (white blood cells). Neupogen can be administered by a health professional as an injection under the skin or intravenously. Some patients can self-inject Neupogen at home. Patients usually receive their first dose of Neupogen a day after their last dose of chemotherapy in each cycle. Side effects from Neupogen can include discomfort described by some patients as an aching in the bones and muscles that can usually be relieved with a non-aspirin pain reliever. Patients who receive Neupogen following a bone marrow transplant may experience nausea, vomiting, rash and hypertension (high blood pressure). Patients need to discuss any side effects and ways to relieve any discomfort with their doctor or nurse.
Because some breast cancers are influenced by the female hormones estrogen and progesterone, estrogen and progesterone receptors should be measured (estrogen receptor assays) in every newly diagnosed breast cancer patient. These tests help predict the risk of recurrence while identifying patients who might benefit from hormonal therapy. Approximately 50% of patients with positive estrogen receptors will respond to some hormonal treatment, while only 10% with negative receptors react favorably. Hormonal therapy may consist of oral administration of drugs such as Tamoxifen (Nolvadex), Megace and Arimidex or by the surgical removal of female hormone secreting glands (e.g., ovaries). Hormonal therapy drugs are designed to change the hormonal environment that many breast cancers need to grow and divide. Hormonal therapy may be used following primary therapy as an adjuvant treatment to decrease the likelihood of cancer recurrence or can be effective by itself in recurrent or metastatic disease. Tamoxifen (Nolvadex) Many breast cancer cells require the hormone estrogen to grow and divide. Tamoxifen works by preventing estrogen from joining with and fueling the growth of breast cancer cells. This can block the cancer from growing and delay recurrence. Tamoxifen works most effectively against tumors that are estrogen-receptor positive and particularly dependent upon estrogen. Breast cancer experts believe that tamoxifen prevents estrogen from reaching cancer cells for only as long as patients are taking it. Current recommendations are for the long-term administration of tamoxifen in patients with positive hormone receptors. Clinical trials have shown that patients taking tamoxifen for at least five years have a lower chance of recurrence than patients taking it for shorter periods of time. If a patient has not gone through menopause, her breast cancer treatment may cause menopause to begin. Menopausal changes can be temporary in younger women but are more likely to be permanent in women who are approaching the age of natural menopause (late forties, early fifties). It is still possible to become pregnant while taking tamoxifen. Women taking tamoxifen should not get pregnant -- it has been associated with fetal damage in laboratory animals. Common side effects include hot flashes, vaginal dryness and in premenopausal women, vaginal discharge and irregular menstrual periods. Vaginal lubrication remains the same or increases in some women. Less common side effects include mood changes and occasional stomach upset. Loss of interest in sex and difficulty with orgasm have also been reported by some women who are taking tamoxifen. Its effects on sexual interest and orgasm are usually reversed after it is discontinued. Chemotherapy combined with Tamoxifen (Chemoendocrine Therapy) Menopausal symptoms and sexual problems may be intensified in women who receive both treatments, especially if they are under the age of fifty. Megace Megace is a progestin (a type of progesterone) that is an alternative to using tamoxifen to prevent the hormonal stimulation of breast tissue that could become malignant. It is usually the drug of choice after
tamoxifen. Megace can also be used to control hot flashes. The most common side effect of Megace is an increase in appetite that can lead to weight gain. Edema and breast tenderness can also occur in patients taking
Megace. Last Updated: 02/12/2003 |
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