Immunochemotherapy with Fludarabine, Cyclophosphamide, and Rituximab Improves Response Rates and Progression-Free Survival of Previously Untreated Pat

Results from this multinational phase III clinical trial presented by during the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, CA (December 6 – 9) by Dr. Michael Hallek, MD from the University of Cologne, Cologne, Germany, and the German CLL Study Group, suggest that fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy may become the new standard first-line therapy for the treatment of advanced chronic lymphocytic leukemia.

In this study, a total of 817 patients with previously untreated chronic lymphocytic leukemia were randomized to receive six 28-day cycles of fludarabine (25 mg/m2 intravenously on days 1 to 3) and cyclophosphamide (FC) (250 mg/m2 intravenously on days 1 to 3) alone or FCR (375 mg/m2 intravenously at start of first cycle and 500 mg/m2 on day 1 for all subsequent cycles). The primary objective of the study was to determine response rates and progression-free survival.

After an average follow-up of 25.5 months, a total of 761 patients were evaluable for response and 787 were evaluable for progression-free survival and overall survival. The overall response rate was significantly higher in the FCR arm (95 percent) as compared with the FC arm (88 percent). The complete response rate was also significantly higher in the FCR arm (52 percent) as compared with the FC arm (27 percent).

At two years, the progression-free survival rate was 76.6 percent in the FCR arm as compared with 62.3 percent in the FC arm. While FCR was found to cause more neutropenia (33.6 percent versus 20.9 percent) and leukopenia (24 percent versus 12.1 percent), it did not increase the incidence of severe infections (18.8 percent versus 14.8 percent) as compared with FC. Taken together, treatment with fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy improves response rate (RR) and progression free survival (PFS) and can be considered a safe first-line treatment for chronic lymphocytic leukaemia.

For more information, read:

• Hallek M, Fingerle-Rowson G, Fink AM, Busch R, et al. Immunochemotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Fludarabine and Cyclophosphamide (FC) Improves Response Rates and Progression-Free Survival (PFS) of Previously Untreated Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL). (Oral Session). Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #325

Also read PubMed Abstracts:

• Borthakur G, O’Brien S, Wierda WG, Thomas DA, et al. Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab--incidence and predictors. Br J Haematol. 2007 Mar;136(6):800-5.