Addition of Cyclophosphamide to Fludarabine Improves Progression-Free Survival

Addition of Cyclophosphamide to Fludarabine Improves Progression-Free Survival in Younger Patients with CLL

According to a recent article published in the journal Blood, the addition of cyclophosphamide (Cytoxan®) to fludarabine (Fludara®) improves anticancer responses, progression-free survival, and time to subsequent treatment among younger patients diagnosed with chronic lymphocytic leukemia (CLL). However, results have not yet indicated that the combination of cyclophosphamide/fludarabine improves overall survival compared to fludarabine alone in these patients.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. The American Cancer Society estimates that approximately 8,000 people will be diagnosed with CLL this year. Currently, there are approximately 60,000 people in the U.S. living with CLL.

CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells that exist in two forms: B- and T-cells. These cells are produced in the bone marrow and each serves a specific function in aiding the body fight infection.

The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal. B-lymphocytes accumulate in the blood, bone marrow, lymph nodes, and spleen. This results in overcrowding of these areas and suppression of the formation and function of blood and immune cells. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the body’s ability to fight infection.

Fludarabine and cyclophosphamide are commonly used agents in the treatment of CLL; either can be used alone as a single agent. Researchers from Germany recently conducted a clinical trial comparing the combination of fludarabine plus cyclophosphamide to fludarabine alone as initial treatment in patients with CLL who were under the age of 66 years. This trial included 375 patients; the majority of participants had advanced disease. Treatment in either group lasted for a maximum of 6 months.

  • Overall anticancer responses were achieved in 94% of patients treated with FC, compared with 83% for those treated with fludarabine alone.
  • A complete disappearance of detectable cancer (complete remission) was achieved in 24% of patients treated with FC, compared with only 7% for those treated with fludarabine alone.
  • Median progression-free survival was 4 years for patients treated with FC, compared to only 20 months for those treated with fludarabine alone.
  • The duration of time during which patients did not require subsequent treatment was one year longer for those treated with FC than for those treated with fludarabine alone (37 months versus 25 months, respectively).
  • No differences in overall survival have been noted as of yet.
  • Treatment with FC resulted in an increased risk of low levels of immune cells and low levels of platelets.

The researchers concluded that initial treatment with FC provides higher response rates, increased duration of progression-free survival, and increased duration without subsequent treatment compared to fludarabine alone as initial treatment for patients under the age of 66 diagnosed with CLL. However, there has been no difference in overall survival time as of yet. Trials comparing the combination of FC as initial therapy for a recurrence to sequential administration of each agent alone are warranted.

Reference: Eichhorst F, Busch R, Hopfinger G, et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006; 107: 885-891.

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