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The two most commonly used types of chemotherapeutic agents for the treatment of chronic lymphocytic leukemia (CLL) are:

• Alkylating agents
• Purine nucleoside analogues

Alkylating Agents

A category of anticancer drugs called alkylating agents have been the mainstay of chemotherapy for CLL for the past 40 years and are usually reserved for CLL patients who have had no prior treatment. The two most commonly used alkylating agents for chronic lymphocytic leukemia are:

• Chlorambucil (Leukeran)

• Cyclophosphamide (Cytoxan) - This drug is often used in combination with other drugs (combination chemotherapy) in CLL patients with Rai stage II, III, or IV disease. Examples of commonly used combination drug regimens for CLL include:

  • CVP - cyclophosphamide + vincristine + prednisone
  • CHOP - cyclophosphamide + doxorubicin + vincristine + prednisone
  • fludarabine + cyclophosphamide

Prednisone, a potent anti-inflammatory corticosteroid drug, is sometimes given in combination with alkylating agents for the treatment of autoimmune hemolytic anemia (AIHA) and/or idiopathic thrombocytopenia that can occur as complications of CLL.

One drawback of using alkylating agents in patients with CLL is that it increases the risk for developing secondary acute myelogenous leukemia (AML) by about 2 to 3 fold.

Bendamustine (Treanda) Approved for Chronic Lymphocytic Leukemia

In March 2008, the U.S. Food and Drug Administration approved an alkylating agent manufactured by Cephalon Inc. called bendamustine hydrochloride (Treanda) for the treatment of chronic lymphocytic leukemia (CLL). In clinical trials, patients with CLL who were treated with bendamustine (Treanda) had a median disease progression-free survival time of 18 months, compared with 6 months for patients who were treated with chlorambucil.

The FDA-approved labeling for bendamustine recommends that the drug be adminstered on the first and second days of a 28-day treatment cycle, with the treatment repeated for up to six cycles. Patients who receive bendamustine must be carefully monitored for both hematologic and non-hematologic toxicities.

Serious side-effects of bendamustine may include:

• Myelosuppresssion in most patients - a decrease in blood counts due to toxicity of the chemotherapeutic agent
• Infections such as sepsis and pneumonia
• Adverse infusion reactions
• Allergic reactions including anaphalaxis
• Tumor lysis syndrome - A side-effect of chemotherapy which results when the tumor is "lysed" or destroyed. It is characterized by symptoms of kidney failure due to excessive amounts of calcium, phosphate,and potassium being released by dying tumors
• Severe skin reactions

Less serious side-effects of bendamustine therapy may include:

• Nausea
• Vomiting
• Diarrhea
• Mild skin rashes
• Itching

Purine Nucleoside Analogues

Purine nucleoside analogues are a class of anti-cancer drugs that have been found to be highly effective for the treatment of CLL. Examples of purine nucleoside analogues that may be used for the treatment of CLL include:

• Fludarabine (Fludara)
• Pentostatin (Nipent)
• Cladribine (Leustatin)

Fludarabine is the most commonly used purine nucleoside analogue for the treatment of chronic lymphocytic leukemia. It is also the drug of choice for patients with refractory CLL who do not respond favorably to initial treatment with alkylating agents. Purine nucleoside analogues may be used alone (monotherapy) or in combination with other drugs in the management of patients with CLL.