Betticher D C, Ratschiller D, Hsu Schmitz S F, von Rohr A, Hess U, Zulian G, Wernli M, Tichelli A, Tobler A, Fey M F, Cerny T
Institute of Medical Oncology, Inselspital, Bern, Switzerland.
Ann Oncol. 1998 Jul;9(7):721-6. doi: 10.1023/a:1008273131598.
To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL).
In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response.
A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P < or = 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1.
Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.
研究2 -氯脱氧腺苷（2 - CDA）即克拉屈滨以24小时静脉输注或皮下推注两种不同剂量给药于复发或难治性慢性淋巴细胞白血病（CLL）患者的疗效及安全性。
在这项非随机的双队列研究中，20例经预处理的CLL患者接受克拉屈滨，剂量为0.7mg/kg/周期，持续静脉输注7天（第1组）；35例患者接受较低剂量0.5mg/kg/周期，皮下推注5天（第2组）。经过两个为期四周的周期后，评估疗效。若疾病进展，则停止治疗；否则最多再给予四个周期治疗直至达到最佳反应。
共进行了130个周期的治疗（第1组41个，第2组89个）。两组患者的特征具有可比性。第1组和第2组的中位剂量强度分别为每周0.172mg/kg和每周0.123mg/kg（P≤0.0001）。所有55例患者的总体缓解率为38%（95%置信区间（95%CI）：25% - 52%），完全缓解（CR）率为5%，部分缓解（PR）率为33%。两组患者的反应相似（第1组为35%，第2组为40%）。未发现克拉屈滨剂量强度与缓解率之间存在关联，既往治疗后复发或难治的患者之间也无差异（24例中的11例与31例中的10例）。两组的中位缓解持续时间均为6个月。第1组的毒性反应，尤其是感染（所有WHO分级，第1组为34%，第2组为7%）和骨髓抑制（1 - 4级中性粒细胞减少，分别为72%和41%的克拉屈滨治疗周期）在统计学上显著更常见。
克拉屈滨对经过大量预处理的慢性淋巴细胞白血病患者有效。剂量降低29%导致相似的反应和缓解持续时间，但显著降低了骨髓毒性和感染风险。以0.5mg/kg/周期皮下推注给药的克拉屈滨是安全的，在该患者群体中不应超过此剂量水平。
