Unfortunately, chemotherapy is associated with a number of side effects, mainly because chemotherapy drugs are toxic to all actively dividing cells, not just cancer cells. Cells in the bone marrow, the lining of the stomach and intestines, and the hair follicles are normally actively dividing. Therefore, chemotherapy may result in a decrease in blood cell counts, nausea, vomiting, diarrhea, and loss of hair. The extent to which a person will experience side effects of chemotherapy depends on many factors, including their stage of disease, physical condition, and the particular chemotherapy regimen being used.

Conventional chemotherapy is also known as standard-dose chemotherapy. Conventional chemotherapy includes chemotherapeutic agents and regimens that have been in use for the past 15 to 40 years. Patients may receive conventional chemotherapy as their only therapy, or they may receive it in preparation for high-dose chemotherapy and stem cell transplant (discussed below).

When conventional chemotherapy is used prior to a stem cell transplant, it is also referred to as induction therapy. The main purpose of induction therapy is to reduce the tumor burden prior to transplant. Certain chemotherapy drugs are more suitable for induction therapy than others. This is because some agents are less toxic to bone marrow cells than others and result in a greater yield of stem cells from the bone marrow. Examples of chemotherapy drugs and regimens suitable for induction therapy for myeloma include dexamethasone, thalidomide/dexamethasone, cyclophosphamide, VAD (vincristine, Adriamycin® [doxorubicin], and dexamethasone), and DVd (Doxil®/Caelyx® [pegylated doxorubicin, Ortho-Biotech], vincristine, and reduced schedule dexamethasone).

Certain chemotherapy drugs are less suitable for use as induction therapy for myeloma. These include several drugs known as alkylating agents, which cross-link to a tumor cell's DNA and ultimately prevent the cell from dividing. Examples of alkylating agents that are less suitable for induction therapy include melphalan and carmustine (BCNU). Although the chemotherapy agent cyclophosphamide is also an alkylating agent, it is suitable for use as induction therapy.

Conventional chemotherapy is typically given in cycles (treatment followed by rest periods). Treatment cycles expose more tumor cells to treatment while they are dividing and allow patients to recover from chemotherapy-related side effects. Chemotherapy is usually administered for approximately 6-12 months or until a patient achieves a plateau response or stable disease, especially if the therapy is well tolerated. When used as induction therapy, usually 3 or 4 cycles are given prior to collection of stem cells. After collection, patients may go straight to a transplant ("early transplantation") or continue to receive chemotherapy until they reach a plateau. In the latter case, the transplant is reserved for when the myeloma relapses ("late transplantation").

The most common chemotherapeutic agent used in myeloma is an oral drug called melphalan. Melphalan is typically given in combination with prednisone, a potent corticosteroid drug with antimyeloma activity. This combination has been a standard treatment for myeloma for the past 40 years and results in a response rate of 50%. Unfortunately, this alkylating agent is less suitable for use as induction therapy especially if high dose therapy and stem cell support is to be considered for future therapy.

Corticosteroids are sometimes used alone as myeloma therapy, especially in older patients and those who cannot tolerate chemotherapy. The most commonly used corticosteroid in this instance is dexamethasone. Corticosteroids may reduce the M protein in up to 60% of previously untreated patients, and in 20% to 40% of patients who have not responded to primary therapy.

Dexamethasone is also used as a form of induction therapy, alone or in combination with other agents. The combination of vincristine, Adriamycin® (doxorubicin), and dexamethasone, also known as VAD, is the most commonly used induction therapy.

The combination of dexamethasone and Thalomid® (thalidomide, Celgene) is an effective initial therapy for myeloma and is suitable for induction therapy. In contrast to VAD, which is administered intravenously, combination thalidomide and dexamethasone (thal-dex) therapy is an oral regimen. Thal-dex is becoming more widely used as initial therapy for myeloma while the use of VAD is decreasing. A recent case-control study showed that thal-dex offers a significantly higher response rate than VAD when used as primary therapy in preparation for a stem cell transplant, however this analysis should be interpreted with caution as this is a retrospective study and several important variables were not reported. (Cavo et al. Blood. 2005; 106(1):35-39.)

New chemotherapy regimens and agents are being investigated for use in myeloma. A promising strategy is the incorporation of novel therapies into standard chemotherapy regimens. For example, agents such as thalidomide and Velcade (bortezomib, Millennium) are being evaluated in combination with melphalan and prednisone in patients who are not candidates for stem cell transplant. Novel agents are also being incorporated into various induction regimens prior to transplant. Examples include Velcade-dexamethasone and Velcade-thalidomide-dexamethasone.

A new formulation of doxorubicin known as Doxil® or Caelyx® (pegylated liposomal doxorubicin) is being evaluated for use in myeloma. This new formulation provides for a slow release of doxorubicin, thus exposing myeloma cells to the drug for a longer period of time. It may also result in an improved toxicity profile due to the potential for use of lower doses of doxorubicin, preferential accumulation of the drug at the tumor site and less exposure to the rest of the body, a shorter infusion time, and less damage to heart muscle, a common complication seen when doxorubicin is given at high doses or over a period of time. The combination of Doxil, vincristine, and reduced dose dexamethasone (DVd) has recently been shown to be effective as induction therapy.

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The table below lists conventional chemotherapy and other drug regimens that are commonly used or under investigation for the treatment of multiple myeloma. Many of these regimens produce similar results, but they differ in various ways, including how fast they work and how well they are tolerated. In addition, these drugs vary in their suitability for use as induction therapy.

The administration of chemotherapy at doses higher than that used with conventional chemotherapy are often used in the treatment of myeloma. This type of chemotherapy is referred to as high-dose chemotherapy. Though more effective in killing myeloma cells than conventional chemotherapy, high-dose chemotherapy also destroys normal blood-forming cells in the bone marrow. Because a person cannot survive without these blood-forming cells, high-dose chemotherapy is always administered in conjunction with a stem cell transplant, which replaces these important cells.

High-dose chemotherapy with stem cell transplantation is used after a patient receives induction therapy (conventional chemotherapy) to reduce the tumor burden. It is often used in younger patients with a good prognosis. Depending on the type of cancer and other factors, some patients may receive one or more treatments of high-dose chemotherapy, possibly in combination with radiation therapy, over a period of several days. This combination of treatments is also referred to as a conditioning regimen. Because this regimen is more intensive than conventional chemotherapy, it is used less frequently in patients over the age of 70, and may not be suitable for patients who have significantly impaired kidney function or performance status, or other coexisting conditions.

Chemotherapy may be used as salvage therapy, that is, treatment for patients who have not responded to primary or subsequent therapy or who experience relapsed disease after an initial response to therapy. A number of regimens are currently used as salvage therapy or are being investigated for this use. If longer than 6 months has passed since a patient had initially responded to primary conventional therapy, the primary therapy can be repeated as salvage therapy following relapse. Various combination therapies are also used. Thalidomide, an oral agent, is also often used as salvage therapy for myeloma patients alone, or in combination with dexamethasone or melphalan and dexamethasone.

Velcade® (bortezomib), a proteasome inhibitor, is approved in the United States for use as monotherapy in myeloma patients who have received at least one prior therapy. It is also approved for use as monotherapy in the European Union for myeloma patients who have received at least one prior therapy and who have already undergone or are unsuitable for stem cell transplantation. Velcade is being evaluated in combination with a variety of chemotherapy agents as salvage therapy.

Examples of salvage regimens are listed in the table below.

Many times a drug may be referred to its common (generic) name, while other times it may be referred to by a brand name or an abbreviation. It may be hard to determine the exact medication being discussed. The following table lists some of the common drugs used in the treatment of myeloma as well as brand names and abbreviations for each.