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Adapted from the NCI Cancer Bulletin, vol. 5/no. 25, Dec. 16, 2008 (see the current issue ³).

Two international phase III studies presented December 2008 at the American Society of Hematology meeting ⁴ in San Francisco show that advanced chronic lymphocytic leukemia (CLL) patients who received the monoclonal antibody rituximab ⁵ (R) in addition to standard chemotherapy with fludarabine ⁶ and cyclophosphamide ⁷ (FC) had outcomes far better than those patients who received FC alone.

The first study ⁸ included 817 previously untreated advanced CLL patients whose mean age was 61 years. They were randomized to receive six 28-day courses of either FC or FCR. After a median follow up of 25.5 months, the complete response rate in the FCR group was 52 percent, compared with 27 percent in the FC group. Progression-free survival was also higher in the FCR group, with 76.6 percent progression-free after two years versus 62.3 percent in the FC arm.

In the second study ⁹, 552 patients (mean age 63 years) with relapsed or refractory CLL were randomized to receive six 28-day courses of FC or FCR. Most of these patients had previously been treated with single-agent alkylator therapy, a purine analog therapy, or combination chemotherapy. Those in the FCR group had a median of 30.6 months without disease progression, compared with 20.6 months in the FC group. Complete response in the FCR group was nearly twice that of the FC group, 24 percent versus 13 percent.

While the overall response with rituximab was better in both studies, negative side effects were more common in the patients who received the drug, including diminished leukocytes and neutrophils. The incidence of these side effects was associated with age, sex, renal function, and the patient's relative health.

"While these studies clearly indicate that rituximab improves both response and progression-free survival when combined with FC, they do not address whether the addition of cyclophosphamide to fludarabine should become the standard chemotherapy platform for the treatment of CLL," cautioned Dr. Wyndham Wilson, head of the Lymphoma Therapeutics Section in the National Cancer Institute's Center for Cancer Research ¹⁰. "The increased toxicity associated with cyclophosphamide requires that physicians weigh the risks and benefits of FCR versus RF."