In order to better follow Crash's treatment for multiple myeloma cancer, it is helpful to understand some of the intrusive symptoms that he may be experiencing, as well as some fundamental explanations about the different treatment aspects themselves. All information has been taken directly from literature published and distributed by the International Myeloma Foundation.

VELCADE® works by inhibiting enzyme complexes called proteasomes.  Both normal cells and cancer cells contain proteasomes, which break down damaged and unwanted proteins into smaller components.  Proteasomes also carry out the regulated breakdown of undamaged protein in the cell, a process that is necessary for the control of may critical cellular functions.  These smaller components are then used to create new proteins required by the cell.  Proteasomes can be thought of as crucial to the cell's "recycling" of proteins.

WHAT IS VELCADE® AND HOW DOES IT WORK?

VELCADE® is the first of a new class of drugs called  proteasome inhibitors.  Because it is a new type of drug, VELCADE® represents a new treatment option for patients who have relapsed on other standard therapies.

When VELCADE® inhibits proteasomes, the normal balance within a cell is disrupted.  This disruption results in a number of effects on the cell, some of which are still being studied.  When proteasomes are inhibited in laboratory tests, cancer cell stop dividing.  They also stop producing chemicals to stimulate other cancer cells.  In additions, inhibition of proteasomes has caused cancer cells to die.  Cancer cells appear to be more sensitive to these effects than normal cells, so that cancer cells die while normal cells can recover.

Clinical studies have investigated the effects of VELCADE® therapy on patients in both the relapsed/refractory and front-line settings.
 

Revlimid® is an immunomodulatory agent.  It is a drug that can modify or regulate the functioning of the immune system.  These agents appear to have multiple actions, including both anticancer and anti-inflammatory activities.  Immunomodulatory agents induce immune responses, enhance the activity of immune cells, and inhibit inflammation.  They are able to alter the levels of various growth factors, called cytokines and/or interleukins, and affect cells of the immune system.  Immunomodulatory agents enhance the activation of specialized white blood cells of the immune system - both the T-cell lymphocytes and T cells known as natural killer cells, or NK-cells - which help kill cancer cells.

Revlimid® is a vascular endothelial growth factor inhibitor.  It belongs to a group of immunomodulatory agents with the ability to inhibit new blood vessel development on which cancer cells depend.  Revlimid® is structurally related to thalidomide but has been modified by researchers to take advantage of the anticancer properties, and at the same time substantially reduce the likelihood of nerve or neurologic toxic side effects (peripheral neuropathy).  Revlimid® has direct and indirect effects on myeloma cells, including the ability to induce programmed cell growth, inhibit new blood vessel growth, and reduce adhesion of myeloma cells to bone marrow stromal cells.  Moreover, Revlimid® can act synergistically with other antimyeloma agents and kill myeloma cells that are resistant to conventional therapy.

What is Dexamethasone, and How Does It Work?

Dexamethasone (also known by the brand names Decadron®, Dexasone®, Diodex®, Hexadrol®, and Maxidex®) is one of the medications used in the treatment of multiple myeloma.  It is a synthetic adrenocortical steroid.  Adrenocortical steroids, also known as glucocorticosteroids or corticosteroids, are produced naturally by the adrenal glands in the body.  To make things less confusing, these compounds will be referred to as the steroids.

Adrenal glands produce hormones and steroids.  The steroids influence any actions of the body's systems.  They are involved in regulation of carbohydrates, proteins, and fats.  They also inhibit inflammatory, allergic, and normal immune responses.  Synthetic versions can imitate the actions of the naturally occurring compounds or replace them in conditions that are associated with insufficient production of much-needed steroids that are normally produced by the adrenal glands.

Dexamethasone, a synthetic steroid, is available in many forms.  It is available as an injection, in oral tablets, in solutions to treat eye infections, in nasal sprays, and in topical forms as a gel, cream, and spray.  The injection and tablets are used to treat multiple myeloma.  Dexamethasone is used to treat a wide variety of medical conditions in addition to multiple myeloma.  Some of these are listed below:

 • Endocrine disorders, including conditions in which the adrenal glands, for numerous reasons, do not produce enough steroids (known as adrenocortical insufficiency and adrenal hyperplasia); thyroiditis (inflammation of the thyroid gland); or hypercalcemia (abnormally high levels of calcium caused by cancer)

• Rheumatic/collagen disorders, including various types of arthritis, ankylosing spondylitis (inflammation of the spine and the sacroiliac joints), systemic lupus erythematosus fungoides (lymphoma involving the skin)

• Dermatologic diseases, including some types of rashes, redness of the skin, and mycosis fungoides (lymphoma involving the skin)

• Allergic states, including those associated with asthma, dermatitis, drug hypersensitivity, perennial and seasonal allergies, and serum sickness.

• Ophthalmic diseases, including a number of conditions that cause redness, swelling, and inflammation of the eyes and surrounding parts of the eyes.

• Gastrointestinal (GI) diseases, such as enteritis (inflammation of the small intestine) and colitis (inflammation of the large intestine)

• Respiratory diseases, including asthma, chronic obstructive pulmonary disease, some types of pneumonia, and sarcoidosis (inflammation of the lymph nodes and other organs)

• Hematologic disorders, including some types of anemia, purpura (bleeding just below the skin), and thrombocytopenia (low levels of platelets in the blood)

• Neoplastic diseases (malignancies), including some types of leukemia, lymphoma, and myeloma.

• Edematous states, including numerous conditions associated with swelling throughout the body

Dexamethasone and other steroids, particularly prednisone, prednisolone, and methylprednisolone, have many uses in the treatment of  cancer.  They suppress certain actions of the immune systems and also inhibit cytokines, which are chemicals in the body decreases inflammation or swelling by stopping white blood cells, which normally fight infection, from traveling to areas of the body where there is swelling.  Its anti-inflammatory  actions can actually stop the swelling around tumors (especially on the spine, brain, and bone) and the resulting pain and other symptoms caused by tumors pressing on nerve endings.

Dexamethasone can also alter normal immune system responses and is therefore useful in the treatment of conditions that affect the immune system, such as certain types of anemia (for example, aplastic anemia and hemolytic anemia), thrombocytopenia, and purpura.

Dexamethasone is useful in the treatment of blood disorders and malignancies such as multiple Myeloma.  It appears to cause programmed cell death, also known as apoptosis.  This means that steroids such as dexamethasone can trigger the destruction of myeloma cells.

Dexamethasone typically is given with other agents - such as vincristine, doxorubicin, and thalidomide - to treat multiple myeloma.  It has been found that steroids can increase the ability of chemotherapeutic and immunomodulatory agents to destroy myeloma cells.  However, dexamethasone and other steroids are sometimes used alone to treat the disease.  In fact, dexamethasone given in high doses, is the most active single agent for treatment of multiple myeloma.  Treatment can sometimes bring about remission.  Dexamethasone thus offers several advantages and benefits.  Response rates typically are high with dexamethasone, but side effects can occur.