Journal of Clinical Oncology, Vol 15, 458-465, Copyright © 1997 by American Society of Clinical Oncology
Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report
JM Sorensen, DA Vena, A Fallavollita, HG Chun and BD Cheson
Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
PURPOSE: To provide fludarabine to physicians for the management of
patients with advanced refractory chronic lymphocytic leukemia (CLL) and to
determine the response rate and duration, toxicity, and survival with this
agent. PATIENTS AND METHODS: This phase II protocol was open to all
eligible patients whose local physicians obtained written permission from
the National Cancer Institute (NCI) to register patients onto 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 assessable 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 median 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 infection in 22%. Neurotoxicity (primarily
grade 1 motor dysfunction) was reported in 14% patients and correlated with
age. CONCLUSION: This study describes the toxicity and activity of
fludarabine in refractory CLL in a setting that more closely resembles
clinical practice than most published trials. The low response rate may be
related to advanced stage (89% Rai high-risk), disease-related symptoms
(63% had B symptoms), and/or degree of prior treatment. Other contributing
factors inherent in a group C treatment protocol included lack of central
pathology review, variable supportive care, and a tendency to use this
mechanism at a later stage in the disease.
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