Betticher D C, von Rohr A, Ratschiller D, Schmitz S F, Egger T, Sonderegger T, Herrmann R, Kroner T, Zulian G B, Cavalli F, Fey M F, Cerny T
Institute of Medical Oncology, University of Bern, Inselspital, Switzerland.
J Clin Oncol. 1998 Mar;16(3):850-8. doi: 10.1200/JCO.1998.16.3.850.
To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine [2-CDA]) administered at two different dosages.
In this two-cohort study, patients with low-grade refractory/relapsing non-Hodgkin's lymphoma (NHL) received 2-CDA at a dose of 0.7 mg/kg per cycle as a continuous intravenous (i.v.) infusion (group 1, n = 44) or at a reduced dose of 0.5 mg/kg per cycle as a subcutaneous (s.c.) bolus injection (group 2, n = 60). Three 2-CDA cycles at > or = 4-week intervals were planned, then treatment could be pursued until six cycles.
A total of 300 cycles were administered (group 1, 114 cycles; group 2, 186). Patient characteristics in both groups were comparable. The median dose-intensities were 0.17 mg/kg/wk and 0.13 mg/kg/wk for groups 1 and 2, respectively (P < or = .0001). The overall response rate for all 104 patients was 54% (95% confidence interval [CI], 45% to 66%; 15% complete response [CR] and 39% partial response [PR]). Response was similar in both patient groups (57% in group 1 and 53% in group 2; P = .72), and no association between 2-CDA dose-intensity and response rate was found (P = .35). Median remission duration was 7 and 12 months in groups 1 and 2, respectively (P = .21). Toxicity, in particular opportunistic infections (> or = grade 2, 30% in group 1 v 7% in group 2; P = .003) and myelosuppression (> or = grade 3 neutropenia, 33% v 8% of 2-CDA cycles, P < .0001), were more frequent in group 1. Multiple logistic regression analysis showed that the infection risk (grade > or = 2) was decreased by 81% with 2-CDA dose reduction in group 2 after adjusting for number of pretreatment regimens and time since diagnosis (P = .01).
When administered as a s.c. bolus injection, 2-CDA at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.
研究两种不同剂量的克拉屈滨（2-氯脱氧腺苷[2-CDA]）的疗效和安全性。
在这项双队列研究中，低度难治性/复发性非霍奇金淋巴瘤（NHL）患者接受2-CDA治疗，第1组（n = 44）以0.7 mg/kg/周期的剂量持续静脉输注，第2组（n = 60）以0.5 mg/kg/周期的降低剂量皮下推注。计划每4周或更长时间进行3个2-CDA周期，然后可继续治疗直至6个周期。
共进行了300个周期的治疗（第1组114个周期；第2组186个周期）。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0.17 mg/kg/周和0.13 mg/kg/周（P≤0.0001）。104例患者的总体缓解率为54%（95%置信区间[CI]，45%至66%；15%完全缓解[CR]，39%部分缓解[PR]）。两组患者的缓解情况相似（第1组为57%，第2组为53%；P = 0.72），未发现2-CDA剂量强度与缓解率之间存在关联（P = 0.35）。第1组和第2组的中位缓解持续时间分别为7个月和12个月（P = 0.21）。第1组的毒性反应，尤其是机会性感染（≥2级，第1组为30%，第2组为7%；P = 0.003）和骨髓抑制（≥3级中性粒细胞减少，2-CDA周期的比例分别为33%和8%，P<0.0001）更为常见。多因素logistic回归分析显示，在调整预处理方案数量和诊断后的时间后，第2组2-CDA剂量降低使感染风险（≥2级）降低了81%（P = 0.01）。
当以皮下推注方式给药时，2-CDA以0.5 mg/kg/周期的剂量是安全的，在该患者群体中不应超过此剂量水平。
