Bi-weekly chlorambucil treatment of chronic lymphocytic leukemia

Abstract

Because the lymphocytes of chronic lymphocytic leukemia (CLL) are known to proliferate slowly, it was postulated that intermittent therapy might have a cumulative inhibitory effect on tumor cells while permitting normal cells to recuperate between doses. Sixty‐two evaluable patients with CLL were treated with chlorambucil given orally as a single pulse every 2 weeks. The initial dose was 0.4 mg/kg; subsequent doses were increased by 0.1 mg/kg until toxicity or disease control was achieved. Responses were obtained in 6 of 8 (75%) previously untreated patients with indolent disease, in 18 of 31 (61%) previously untreated patients with active disease, in 7 of 14 (50%) previously treated patients not shown to be resistant to alkylating agents, and in 2 of 9 (22%) patients resistant to prolonged daily chlorambucil therapy. The over‐all effectiveness in patients with CLL not previously resistant to chlorambucil was 31 of 53 (58%), with five complete remissions (9%). Hematologic toxicity was usually mild and never life‐threatening. Gastrointestinal toxicity, which occurred in 23 of 62 patients, was usually mild and easily controlled with anti‐emetics. It is concluded that bi‐weekly oral administration of chlorambucil is effective therapy for CLL with response rates similar to daily continuous chlorambucil. Hematologic toxicity is considerably less than with daily treatment.

Long-term Outcomes in Patients with Chronic Lymphocytic Leukemia Treated with Standard Therapy

“…Initial cures through CL, in our studies, are comparable to those reported by other authors (69%). CF efficiency is also comparable to other reports (80%) [34,35]. The best responses, with first-line treatment, were obtained with CFR, a known observation [36] SLP, after the initial treatment, was also better with CFR and matches other studies [36,37] .…”

Outcome of advanced chronic lymphocytic leukemia following different first-line and relapse therapies: a meta-analysis of five prospective trials by the German CLL Study Group (GCLLSG)

“…1 After the use of monotherapies such as chlorambucil over several decades, [2][3][4] significant improvements in response rates and progression-free survival (PFS) were achieved with purine analog-based combination therapies [e.g. fludarabine and cyclophosphamide (FC)].…”

Fludarabine phosphate for the treatment of low grade lymphoid malignancy

“…Thereafter, although repeated responses may be achieved, the majority of patients die as a consequence of the disease. The alkylating agents, chlorambucil and cyclophosphamide, when used alone, may induce response rates of up to 60% in previously untreated patients with CLL (Knospe et al, 1974;Huguley, 1977;Sawitsky et al, 1977) but lower response rates with a shorter duration of remission are the rule for subsequent therapy (Oken & Kaplan, 1979;Montserrat et al, 1986). Similarly, in follicular NHL, response rates to single agent chemotherapy at presentation and at first and second recurrence remain about 65-70% (Israels et al, 1958;Ezdinli & Stutzman, 1965;Jones et al, 1973;Anderson et al, 1982) but, thereafter, therapy becomes rapidly less satisfactory (Gallagher et al, 1986).…”