Myeloma (cont.)

Medications

Numerous chemotherapy and biological drug combinationshave been used for multiple myeloma.Which type and combination of therapy depends on many factors, including the type and stage of myeloma, the ability to tolerate chemotherapy side effects, and if any previous treatment was rendered or if further treatment is planned,such as stem-cell transplantation. Hematologists/oncologists often work together regionally to decide which combination of chemotherapy and biological drugs are currently working best for their patients. Because of this regional collaboration, the drug combinations often vary and are able to change rapidly when improved results occur.

Chemotherapy

• Combinations of different chemotherapy drugs seem to be more effective than single agents.Several drugs with different mechanisms of action, when given together at lower doses, will likely increase the effectiveness of treatment, while reducing the likelihood of intolerable side effects.
  
  
• Several different standard combinations are used as induction therapy in myeloma, but the most widely used is the combination of vincristine (Oncovin), doxorubicin (Adriamycin), and the corticosteroid, dexamethasone (Decadron). This combination of drugs is referred to as "VAD". Another widely used combination is oral melphalan (Alkeran) with the corticosteroid prednisone. Which combination a person is given depends on the treatment plan and the experiences of the specialist and the medical center where treatment is received. For example, if a stem-cell transplant is part of a treatment plan, melphalan may not be given, since it can lower stem cell production.
  
  
• Recently, a new drug that interferes with cancer cell proteins (proteasome inhibitor), called bortezomib (Velcade) has been approved for second-line therapy. Studies are underway to determine its effect in first-line treatment and in combination with chemotherapy (see New drug therapy).
  
  
• The combinations of drugs are usually given according to a set schedule that must be followed strictly.
  
  
• In some situations, chemotherapy can be given in the hematologist-oncologist's office. In other situations, theperson may need to stay in the hospital.

Chemotherapy is given in cycles.

• One cycle includes the period of actual treatment (usually several days) followed by a period of rest and recovery (usually a few weeks).
  
  
• Standard treatment typically includes a set number of cycles, such as 4 or 6. Spacing out the chemotherapy this way allows a higher cumulative dose to be given while improving the person's ability to tolerate the side effects.

Chemotherapy may be given in pill form, but usually is in liquid form to be infused directly intothe bloodstream through a vein (intravenous).

• Certain drugs widely used against myeloma-namely, melphalan, prednisone, dexamethasone, and new time-release forms of doxorubicin-are in pill form.
  
  
• Most people who receive intravenous (IV) chemotherapy will have a semi-permanent device placed in a vein, usually in the chest or upper arm.This device allows a person's medical team quick and easy access to blood vessels, both for administering medications and for collecting blood samples. These devices come in several types, usually referred to as "catheter," "port," or "central line."

Other drug therapy

Other drugs that are standard treatments for myeloma are corticosteroids (prednisone or dexamethasone) and thalidomide (Thalomid).

Corticosteroids are powerful drugs that have many different actions, including anti-inflammatory and anti-immunity activity. They are active against myeloma and reduce production of protein M. Prednisone is usually given with melphalan. Dexamethasone can be given with chemotherapy agents or alone for people who cannot tolerate chemotherapy drugs. It is also given with thalidomide.

A nonchemotherapeutic agent, thalidomide, has been increasingly used in the first-line treatment of multiple myeloma.This is considered an immunomodulatory agent and is usually given with a corticosteroid, such as prednisone or dexamethasone (Decadron).Thalidomide's actions may include decreasing the ability of cancer spread throughout the blood (antiangiogenesis), interfering with adhesion molecules, or enhancing release of cytokines (cancer fighting substances within the body). This drug may be associated with sleepiness, constipation, venous blood clots, and numbness and tingling in the tips of the extremities.It is absolutely contraindicated in pregnancy, as it causes birth defects. The drug is dispensed through a program that ensures that physicians have educated patients about the importance of contraception when taking the drug. Usually, aspirin or low-dose blood thinners, such as warfarin (Coumadin) are given in conjunction with thalidomide and corticosteroids.

New drug therapy

A new analogue of thalidomide, CC-5013, or lenalidomide (Revimid), purportedly has fewer side effects of thalidomide and appears to be more potent than thalidomide in laboratory studies. It is also an immunomodulatory agent, which has undergone early clinical evaluation for recurrent myeloma and newly diagnosed myeloma with encouraging results. Further clinical evaluation is necessary and ongoing. It has been evaluated as part of combined therapy with corticosteroids or chemotherapy drugs. Currently, other immunomodulatory drugs for myeloma are also undergoingdevelopment.

Bortezomib (Velcade) is the first of a new class of medicines called proteasome inhibitors.Proteasome inhibitors may preferentially disrupt a cancer cell's growth.It is currently approved for refractory myeloma, which has previously been treated with two other regimens.However, promising results from early clinical trials suggest that it may be more effective when used for earlier disease.Currently, clinicaltrials are underway to assess results for first-line treatment, and also to evaluate combination therapy using the drug with corticosteroids, other chemotherapy drugs, and thalidomide. Other proteasome inhibitors have recently been developed and are now undergoing early clinical evaluation.