engleski

Fludarabine vs. High dose continuous chlorambucil : Interim analysis of a randomized phase II study in untreated B-cell chronic lymphocytic leukemia (B-CLL)

Background: In the last few years the emerging role of Fludarabine (FAMP) in the treatment of B-CLL has been demonstrated. More recent studies indicate the superiority of this drug towards standard dose chlorambucil (SD-CLB) or combination chemotherapy, so far only in terms of response rate and duration of response. On the other hand two subsequent randomized trials demonstrated a higher efficacy of high dose continuous chlorambucil (HD-CLB) over both intermittent SD-CLB and combination chemotherapy. Design of the Study: In 1993 the EORTC-LCG activated a randomized study comparing HD-CLB and FAMP in untreated B-CLL patients with advanced disease as defined by elevated Total Tumor Mass score (TTM) [Jaksic et al. Br J Haematol 1981, 49: 405] and/or bone marrow failure. Stage was also assessed according to the International Workshop CLL criteria. Patients over 75 years and those with severe concomitant diseases were ineligible. HD-CLB and FAMP were both administered for 18 weeks. HD-CLB consisted of 10 mg/mČ2/day, with dose reduction based on peripheral cell count, according to toxicity-tailored therapeutic schedule. FAMP was used at the dose of 25 mg/mČ2/day for 4 consecutive days every 3 weeks for 6 courses. Non responding patients were crossed to alternate regimen and responding cases did not receive any further therapy. The main end-points of the study were clinical, bone marrow and phenotypic response rate, toxicity and survival. Criteria of response were defined according to the recommendations of the NCI-sponsored working group and by TTM reduction. Results: At the date of the present interim analysis (August 1996), 67 patients were randomized and 40 were evaluable for response and toxicity, with a median follow-up of 11 months. Median age was 61 (45), 57.5% were males, median TTMsize was 10.9 (8.8), and distribution of patients in Rai stage 0, I, II, III, IV was 3, 8, 19, 6 and 4, respectively. Grade 3/4 overall hematological toxicity was observed in 74% and 52% of cases treated with HD-CLB and FAMP, respectively. Non hematological toxicity consisted of allergy in 2, hepatic in 4, renal in 1 and major infection in 3 patients. The treatment was stopped because of toxicity in 4 and 3 cases receiving HD-CLB and FAMP, respectively. The overall clinical response rate was 45% CR, 32.5% PR and 22.5% were non responding. Five deaths have been reported so far. Conclusions: This interim analysis indicates the feasibility of both regimens in advanced B-CLL with an overall clinical response higher than 75%. A longer follow-up is necessary to draw definite conclusions on the different impact of these treatments on response rate and survival.

chronic lymphocytic leukaemia; therapy

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