Activity of oral fludarabine phosphate in previously treated chronic lymphocytic leukemia

Purpose: A prospective, multicenter open-label phase II clinical trial was conducted to assess the efficacy and safety of oral fludarabine phosphate. Reference to an historical group of patients treated with the intravenous ( IV) formulation allowed the investigators to compare the two formulations. Patients and Methods: Efficacy was assessed using the International Worksho p on Chronic Lymphocytic Leukemia (IWCLL) and National Cancer Institute (NC I) criteria for complete remission (CR), partial remission (PR), stable dis ease, or disease progression. Safety monitoring included World Health Organ ization (WHO) toxicity grading for all adverse events. Results: Seventy-eight (96.3%) of 81 recruited patients with previously tre ated B-cell chronic lymphocytic leukemia (CLL) received 10-mg tablets of fl udarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. According to IWCLL criteria, the overall remission rate was 46.2% (CR, 20.5%, PR, 25.6%). The comparative f igures using NCI criteria were 51.3% (CR, 17.9%, PR, 33.3%). Overall, 30 in cidents of severe adverse events were reported for 22 patients. WHO grade 3 or grade 4 hematologic toxicities included granulocytopenia (53.8%), leuko cytopenia (28.2%), thrombocytopemia (25.6%), and anemia (24.4%). Gastrointe stinal adverse events were more common with the oral formulation than previ ously reported Vith IV fludarabine phosphate. However, these events were ge nerally mild to moderate. Conclusion: This study demonstrates that oral fludarabine phosphate has sim ilar clinical efficacy to the IV formulation and a safety profile that is b oth predictable and essentially similar to that of the IV formulation. (C) 2001 by American Society of Clinical Oncology.