2-Chlorodeoxyadenosine (2-CdA) in 2-Hour Versus 24-Hour Intravenous Infusion in the Treatment of Patients with Hairy Cell Leukemia

Abstract

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial

“…5,11 Fifty-four patients were required to be assigned to each treatment arm to detect a decrease of 25% from a 75% CR rate, with error levels of ␣ ϭ 0.05 and ␤ ϭ 0.2 for a 2-sided test. Taking into account possible drop-outs, accrual was increased by 20%, resulting in a requirement of 65 patients per arm.…”

“…In chemotherapy-naive HCL, one course of 2-CdA induces complete response (CR) and long-term survival in the vast majority of patients. [1][2][3][4][5] Given this considerable clinical efficacy, the major challenge regarding 2-CdA therapy is reduction of side effects, especially severe infections that may lead to septic death. Lauria et al 6 suggested that a novel schedule based on 6 weekly 2-hour 2-CdA infusions could be as effective as the standard 7-day and 5-day protocols but associated with less neutropenia and fewer life-threatening infections.…”

2-Chlorodeoxyadenosine (Cladribine) in the treatment of patients with chronic lymphocytic leukemia 55 years old and younger

“…[27][28][29] The efficacy of 2-CdA given as a 2-h vs a 24-h infusion was essentially the same also in hairy cell leukemia. 30 Pharmacokinetics studies confirm the effectiveness of 2-CdA given as 2-h bolus for shorter periods of time, ie for 5 instead of 7 days. 31,32 Taking into account that a 2-h infusion is more convenient and may be given on an out-patient basis, our results seem to be important from a practical point of view.…”

Hairy cell leukemia

“…Standard dosage 0.09 mg/kg by continuous intravenous infusion for 7 days. Small studies suggest that similar responses may be obtained with simpler regimens, eg, 0.1 mg/kg intravenously over 2 hours daily x 5 to 7 days or 3.4 mg/m 2 SC OD x 7 days [21,22]. A weekly regimen, 0.15 mg/kg x 6, also appears to be effective and less likely to cause neutropenic fever and the need for transfusions [24].…”

“…For CdA, the original treatment regimen was 0.09 mg/kg/d x 7 by continuous infusion, and this remains the standard. However, to simplify the regimen for outpatient management, CdA has been administered subcutaneously or as 2-hour boluses daily for 5 to 7 days, and the remission rates appear equivalent [21,22] (Table 1). To decrease the incidence of febrile neutropenia, Lauria et al [24•] have treated 30 patients with a less intensive weekly regimen of CdA, ie, 0.15 mg/kg intravenously weekly x 6.…”