TREATMENT OF REFRACTORY CHRONIC LYMPHOCYTIC-LEUKEMIA WITH FLUDARABINEPHOSPHATE VIA THE GROUP-C PROTOCOL MECHANISM OF THE NATIONAL-CANCER-INSTITUTE - 5-YEAR FOLLOW-UP REPORT

Purpose: To provide fludarabine to physicians for the management of pa tients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival w ith this agent. Patients and Methods: This phase II protocol was open to all eligible patients whose local physicians obtained written permi ssion from the National Cancer Institute (NCI) to register patients on to this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. Results: Thirty-two percent of assessabl e patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response, The median duration of response was 13.1 months and the med ian survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infe ction in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 74% patients and correlated with age. Conclusion: This stu dy describes the toxicity and activity of fludarabine in refractory CL L in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced st age (89% pal high-risk), disease-related symptoms (63% had B symptoms) , and/or degree of prior treatment, Other contributing factors inheren t in a group C treatment protocol included lack of central pathology r eview, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.