Chemotherapy Agents

Chemotherapy is the use of medicines to destroy cancer cells. Most chemotherapy agents target rapidly dividing cancer cells, although they often affect healthy cells as well. Chemotherapy can be given as a monotherapy (single medication) but is often given in combination with treatments like steroids, or targeted therapies such as proteasome inhibitors.

Here are some of the chemotherapy agents that are now being used, or may be used, to treat myeloma.


Bendamustine is a purine analog that is used in combination with a corticosteroid called prednisone to treat newly diagnosed multiple myeloma patients. Bendamustine works both as a purine analog and as an alkylating agent to prevent DNA from replicating, which results in cell death.

Some of the common side effects of bendamustine therapy include skin rash, chills, fever, pneumonia, itching, and neutropenia.


Cisplatin is a platinum-containing chemotherapy agent used in treating a variety of cancers. Cisplatin binds to DNA and prevents its repair, eventually leading to cell death. The activity of cisplatin is further enhanced by the use of other chemotherapy agents, such as etoposide.

Cisplatin in combination with dexamethasone, cyclophosphamide, and etoposide has been shown to be effective as a salvage therapy for patients with relapsed or refractory multiple myeloma. Such use could allow for better outcomes in patients about to undergo another round of AHSCT.

Side effects of cisplatin can include joint pain, loss of balance, fatigue, hearing loss, seizures, swelling in the legs, muscle cramps, fever, hoarse throat, and unusual bruising.


Cyclophosphamide is an alkylating agent that affects DNA replication, thereby preventing cell division. The activation of the treatment happens in the liver, where it is converted into an active form called aldophosphamide. Cyclophosphamide is often used in combination with Velcade (bortezomib) or dexamethasone as a first-line treatment for multiple myeloma.

To treat a cancer relapse, cyclophosphamide is typically given in combination with Revlimid (lenalidomide), dexamethasone or Pomalyst (pomalidomide), and dexamethasone.

Cyclophosphamide can cause several side effects, including nausea, vomiting, loss of appetite, diarrhea, hair loss, swelling in the legs, and painful urination.


Cytarabine, also known as cytosine arabinoside, is an antimetabolite chemotherapy agent that works by killing cells in which DNA is being actively synthesized.

Common side effects of cytarabine therapy include fatigue, amenorrhoea (halting of regular menstruation in women), and injection-site reactions. Other possible side effects include hair loss, loss of appetite, bruising, abdominal pain, and pericarditis.

In rare cases, patients may experience cytarabine syndrome, a combination of symptoms such as fever, muscle and bone pain, rash, sore eyes, and extreme weakness.


Doxorubicin is an anthracycline and a commonly used chemotherapy agent in the treatment of many types of cancers, including multiple myeloma. Doxorubicin is thought to work by binding to an enzyme called topoisomerase 2 that is involved in DNA replication and blocking its activity, leading to cell death. Another proposed mechanism is that doxorubicin treatment increases the production of ceramides, a type of fat inside the cells, which prevents cell division through a series of downstream events.

To treat multiple myeloma, doxorubicin is often used in combination with Velcade in patients not previously given Velcade. Side effects of this combination include neutropenia, thrombocytopenia, anemia, fatigue, hand-foot syndrome, loss of appetite, and diarrhea.

Doxorubicin is also available as a pegylated liposomal formulation marketed by Janssen as Doxil in the U.S. This formulation helps in the slow the drug’s release in the body and reduces side effects.


Etoposide is a toxin derived from the Mayapple plant. It works by binding to topoisomerase 2 and blocking its activity, resulting in breaks in the DNA. This prevents cell division and leads to cell death.

Etoposide treatment is associated with side effects that include an increased risk of infection, bruising and bleeding of gums due to thrombocytopenia, anemia, loss of appetite, constipation, peripheral neuropathy causing numbness or tingling in the hands or feet, and a sore throat.

Regular tests of blood cell counts are likely to be required while using this chemotherapy.


Idarubicin is an anthracycline that is used as a chemotherapy agent in several cancers, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), metastatic breast cancer, and multiple myeloma. Idarubicin in combination with cyclophosphamide and dexamethasone was shown to be effective as induction therapy for AHSCT-eligible patients.

Idarubicin attaches to DNA to inhibit the activity of topoisomerase 2, preventing the attachment of DNA fragments during replication. This arrests cell division and causes cell death.

Idarubicin’s use can cause side effects such as thrombocytopenia, a risk of infection, breathlessness, sores in the mouth and throat, diarrhea, and, in rare cases, changes in heart rate.


Melphalan is an alkylating agent that is used as palliative chemotherapy for symptom relief in multiple myeloma patients. At higher doses, it is also used as a standard conditioning regimen during autologous hematopoietic stem cell transplantation (AHSCT).

Melphalan is potent against rapidly dividing cells, such as myeloma cells, but it can also affect healthy blood-forming cells in the bone marrow. Patients using it are at a greater risk of infection, bleeding, and anemia, and require constant monitoring of blood counts and hemoglobin levels.


Last updated: Jan. 21, 2019


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