A Phase III Clinical Study of Treatment of Patients with Chronic Lymphoproliferative Disorders (CLPD) with Fludarabine, Cyclophosphamide, and Rituximab (FCR) Combination.

Background: The treatment of patients with chronic lymphocytic leukemia (CLL) with Rituximab in combination with fludarabine and cyclophosphamide was reported to be more efficacious, in terms of complete and molecular remission compared with historical data for fludarabine plus cyclophosphamide (

Aims: Evaluation of the clinical efficacy and toxicity of the FCR combination in patients of our Haematologic Centre.

Methods: Seventeen patients, 8 males and 9 females with a median age of 69,5 years, with relapsed/refractory or de novo CLPD (9 CLL and 8 NHL patients) were enrolled in this study between February 2002 and August 2004. Fifty percent of CLL patients had Rai stage I/II and the rest 50% had Rai stage III/IV disease. Four NHL patients had an International Prognostic Index (IPI) 2, one patient IPI 3 and three patients IPI 4. All patients were treated with Rituximab 375 mg/m2 on day1 in combination with Fludarabine and Cyclophosphamide (25 mg/m2 and 250 mg/m2 respectively) for days 2 to 4, every 4 weeks, for 6 consecutive cycles. Nine patients had a history of a prior unsuccessful treatment.

Results: Overall, 14 out of 17 evaluable patients (82%) were responsive to the treatment [12 patients (70%) complete response (CR) and 2 patients (12%) partial response (PR)]. The remaining 3 patients had progressive disease (NR). Hematological toxicity was acceptable (grade 2–3 neutropenia in 6/17 patients, grade 2–3 anemia and thrombocytopenia in 2/17 patients). There were no septic episodes except one case with neutropenic fever. There were no adverse events like nausea or vomiting except one patient with a serious anaphylactic reaction due to Rituximab administration. Three CLL patients died because of progressive disease.

Summary/conclusions: this preliminary report suggests that the FCR regimen is an effective and safe treatment for CLPD patients, achieving higher CR rates than previous treatments. A longer follow up of a larger number of patients is required to confirm an improved survival in these patients.