Thursday, July 8, 2010

Drugs Used to Treat Bone Metastases

Drugs Used to Treat Bone Metastases

When breast cancer spreads past the breast and axillary (armpit) lymph nodes, it often spreads first to the bone. These breast cancer tumors in the bone are called "bone metastases." As advanced breast cancer dissolves portions of bone, a variety of problems can occur. Bone metastases can cause pain, decreased activity, and potentially severe problems such as fractures. Other complications that can arise from bone metastases include the surgical treatment for fractures, hypercalcemia (abnormally high levels of calcium), and spinal cord compression (vertebral damage due to pressure on the spinal cord). A class of drugs called bisphosphonates can beneficial for breast cancer patients whose cancer has spread to the bone.
Bisphosphonates are currently used to help treat osteoporosis, a degenerative bone disease affecting mainly post-menopausal women. In patients with osteoporosis, the bone loses a significant portion of its density, greatly increasing the risk of serious fractures.
Types of bisphosphonates that may be helpful in treating bone metastases include:
  Click here for profiles of individual breast cancer drugs.

Chemotherapy drugs—alkylating agents:

Chemotherapy drugs—alkylating agents:

Alkylating agents are a certain group of chemotherapy drugs that target the DNA of cancer cells to prevent the cells from growing or reproducing. Alkylating agents attack cancer cells in all phases. The drug Cytoxan (generic name, cyclophosphamide) is a common alkylating agent used to treat breast cancer. Cytoxan is typically used in combination with other chemotherapy drugs.

Chemotherapy drugs—taxanes:

Chemotherapy drugs—taxanes:

Taxanes are a certain group of chemotherapy drugs that prevent cancer cells from dividing. Taxanes affect microtubules of cells, which are normally formed when cells divide. Normally, once cells stop dividing, the microtubules are broken down. However, taxanes stop microtubules from breaking down, thereby "clogging" cancer cells with microtubules so they cannot divide. The drugs Taxol (generic name, paclitaxel) and Taxotere (generic name, docetaxel) are examples of taxanes used to treat breast cancer. Taxanes are often used in combination with other chemotherapy agents.

Classes of Chemotherapy Drugs Used to Treat Breast Cancer

Classes of Chemotherapy Drugs Used to Treat Breast Cancer

Class Action Examples
Anthracyclines Deform DNA structure of cancer cells Adriamycin (doxorubicin) Ellence (epirubicin)
Taxanes Prevent cancer cells from dividing Taxol (paclitaxel)
Taxotere (docetaxel)
Alkylating Agents Target DNA of cancer cells Cytoxan (cyclophosphamide)

Chemotherapy drugs—anthracyclines:

Anthracyclines are a certain group of chemotherapy drugs. While anthracyclines can be very effective against breast and other cancers, they pose a risk of cardiotoxicity (severe heart problems) and therefore, they are typically used in limited doses. Patients should also be closely monitored for any heart problems during treatment. Anthracyclines work by deforming the DNA structure of cancer cells and terminating their biological function. The drugs Adriamycin (generic name, doxorubicin) and Ellence (generic name, epirubicin) are examples of anthracyclines used to treat breast cancer. Anthracyclines are commonly used in combination with other chemotherapy drugs to help decrease the risk of side effects.

Biologic response modifiers:

These drugs bind with certain proteins on breast cancer cells, preventing their growth. The drug Herceptin (generic name, trastuzumab) is a monoclonal antibody that attaches itself to HER2 (also written HER2/neu), a protein found on breast cancer cells. Approximately 30% of breast cancer patients have extra copies of the HER2 protein, which can signal more aggressive cancers. Herceptin binds to HER2 receptors on breast cancer cells, preventing them from growing and dividing. Herceptin is only indicated for breast cancer patients who overexpress the HER2 protein. Patients should be tested for HER2 expression to determine whether Herceptin is a viable treatment option. Other hormonal therapies: Hormone therapies are used to treat breast cancers that are dependent on estrogen for survival. In addition to SERMs and aromatase inhibitors, there are several other hormonal therapies used to treat breast cancer. For example, the drug Zoladex (generic name, goserelin acetate) is a synthetic form of the body’s lutenizing hormone-releasing hormone (LHRH). Zoladex blocks the release of estrogen in breast cancer patients (and testosterone in prostate cancer patients), preventing breast and prostate cancer cells from growing.
Another hormone therapy, Faslodex (generic name, fulvestrant), appears to be effective for women who have become resistant to tamoxifen, according to recent studies. Instead of binding to estrogen receptors in breast cancer cells like tamoxifen, Faslodex destroys estrogen receptors in cancer cells.

SERMs (selective estrogen-receptor modulators):

These drugs bare a chemical resemblance to the hormone estrogen. Many breast cancers are "estrogen-dependent," meaning that they depend on estrogen in order to survive and reproduce. Because SERMs mimic estrogen, they are able to bind to estrogen receptors in breast cancer cells. By binding to these receptors, they block estrogen from breast cancer cells, thereby starving the cancer cells. Tamoxifen is currently the most commonly prescribed SERM. Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) to help treat both early and advanced stages of breast cancer. Recently, tamoxifen also received FDA approval for use in post-menopausal women at high risk of breast cancer after a large clinical trial showed that tamoxifen could reduce the risk of breast cancer by 49%. The drug Fareston (generic name, toremifene) is another SERM used to treat advanced breast cancer.
Another SERM, Evista (generic name, raloxifene) is used to treat osteoporosis, a degenerative bone disease. In clinical trials, raloxifene was shown to reduce the risk of breast cancer in high-risk post-menopausal women by 44 to 71 percent.
Researchers are also investigating another SERM called arzoxifene for the treatment of breast cancer. Arzoxifene is made by the same company as raloxifene (Eli Lilly and Company) and is described to be a next-generation SERM. The drug is currently in Phase III clinical trials.

Aromatase inhibitors:

These drugs work by binding to the body’s aromastase enzyme, an enzyme responsible for producing estrogen. Many breast cancer cells depend on estrogen to grow and multiply quickly. Once the aromatase inhibitor has binded to the aromastase enzyme, estrogen cannot be produced by the enzyme. This lack of estrogen starves cancer cells, preventing them from growing and dividing. There are several aromatase inhibitors that are used to help treat advanced breast cancer including:
  • Aromasin (generic name, exemestane)
  • Femara (generic name, letrozole)
  • Arimidex (generic name, anastrozole) 
  • Megace (generic name, megestrol)
Recent studies suggest that some aromatase inhibitors may be more effective than tamoxifen in treating advanced breast cancer or may be useful after patients become resistant to tamoxifen. For example, Femara was recently FDA approved as an initial treatment option in advanced breast cancer patients after data showed that Femara may work better than tamoxifen in some patients (i.e., slows the growth of cancer and improves survival time). Recent studies also show that both Arimidex and Femara many be more effective than Megace for treating breast cancer.