HOUSTON—The combination of fludarabine (Fludara) and cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar) plus rituximab(Drug information on rituximab) (Rituxan), known as FCR, produces "a higher complete remission rate than prior regimens tested" against chronic lymphocytic leukemia (CLL), reported William Wierda, MD, of the department of leukemia at The University of Texas M. D. Anderson Cancer Center in Houston. In addition, molecular remissions can be demonstrated in a significant number of those responding to the FCR combination.
Among a group of 135 patients receiving six cycles of FCR, 63% of the patients achieved complete remission and the overall response was 95%. To determine the level of molecular remission, polymerase chain reaction (PCR) assay was performed on the bone marrow of 55 of the 85 patients achieving complete remission, and 56% were negative. Negativity was also demonstrated in the bone marrow of 6 out of 10 partial responders assayed (out of a total of 23). Five of those six patients were in partial remission due to anemia or low platelet or neutrophil counts, and "none of the five had morphologic evidence of residual disease," Dr. Wierda reported.
PCR was performed on both blood and marrow on some patients achieving complete or partial remission. "There was a strong correlation between blood and marrow," Dr. Wierda said, "and the discordance rate was less than 10%."
Updated Data Presented
"The increased activity of fludarabine combined with cyclosphosphamide, and the potential for chemosensitization between purine analogs, alkylating agents, and monoclonal antibodies, is the rationale for combining these agents in a trial to determine the efficacy." Dr. Wierda explained.
Data presented on the FCR study last year included only 53 patients, while the updated data include 135 patients. All were "required to have an indication for treatment according to National Cancer Institute working group criteria," Dr. Wierda said. In addition, patients could have had no prior therapy for CLL, a performance status of 3 or less, and adequate hepatic and renal function.
Six cycles of FCR were administered. In the first cycle, patients received rituximab at the standard dose of 375 mg/m² on day 1. In subsequent cycles, rituximab was administered at the higher dose of 500 mg/m² on day 1. Fludarabine at 25 mg/m² and cyclophosphamide at 250 mg/m² were given on days 2 to 4 of cycle 1 and days 1 to 3 of cycles 2 to 6.
