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Of the various purine nucleoside analogues available, doctors have had the most experience with fludarabine which is the most commonly used in patients with CLL. Studies have shown that:

• Fludarabine monotherapy for CLL is very effective with most patients achieving a positive response to the drug.

• Fludarabine monotherapy is also very effective for the treatment of patients with relapsed CLL.

• Fludarabine has been found to be more effective than chlorambucil in studies comparing response rates and disease-free time intervals in patients with CLL.

• Studies have also shown that fludarabine monotherapy is more effective than combination chemotherapy with CHOP or CVP in previously untreated CLL patients.

• Fludarabine has also been found to be very effective when used in combination with an alkylating agent (e.g., cyclophosphamide) or a monoclonal antibody (rituximab) in patients with CLL.

Potential complications of fludarabine therapy include the risk of developing severe autoimmune hemolytic anemia as well as an increased risk for opportunistic infections such as Pneumocystis carinii pneumonia and Herpes virus infections. Patients with CLL who are being treated with fludarabine and corticosteroids (e.g., prednisone) are also usually treated with a prophylactic antibiotic (e.g., sulfmethoxazole/trimethoprim) and an antiviral agent (e.g., acyclovir) to prevent opportunistic infections.

A study published in 2002 in the Journal of Clinical Oncology (Volume 20; pages 3878-3884) reported that patients with CLL who were treated with fludarabine and chlorambucil were at increased risk for developing myelodysplastic syndromes (MDS) and/or acute myelogenous leukemia (AML). The increased risk for developing MDS and/or AML has not, however, been reported in clinical trials using combinations of:

• fludarabine and cyclosphosphamide
• cladribine and cyclophosphamide
• cladribine and chlorambucil

Side-Effects of Chemotherapy

A drawback of chemotherapy for the treatment of cancer is that it can produce a variety of undesired side-effects. The side-effects of chemotherapy vary depending upon the type of drug(s) used, the dosage, and the length of time that the chemotherapy is administered. In general, common side-effects of cancer chemotherapy may include:

• Hair loss
• Mucositis - inflammation of the lining of the mouth and gastrointestinal tract, which can be very painful.
• Increased susceptibility to infections
• Increased susceptibility to bleeding and bruising
• Fatigue and general loss of energy
• Nausea and vomiting
• Loss of appetite

The side-effects of cancer chemotherapy are temporary and usually disappear after treatment has been completed. A variety of strategies are available to better control the side-effects of chemotherapy and patients should discuss with their oncologist the various options that can be used to minimize or reduce these adverse side-effects.