Kalinka-Warzocha Ewa, Wajs Jaroslaw, Lech-Maranda Ewa, Ceglarek Bernadetta, Holowiecki Jerzy, Federowicz Irena, Walewski Jan, Czyz Jaroslaw, Robak Tadeusz, Warzocha Krzysztof
Department of Proliferative Diseases, Regional Oncology Center, Lodz, Poland.
Cancer. 2008 Jul 15;113(2):367-75. doi: 10.1002/cncr.23558.
The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low-grade B-cell non-Hodgkin lymphoma (LGNHL).
For this 3-arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study.
Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7-9,3; P = .002, and OR = 8.5; 95% CI, 3.2-22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8-18.5; P = .003; and OR = 14; 95% CI, 4.4-44; P < .0001, respectively), progression-free survival (log-rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine-containing regimens remained an independent prognostic factor for progression-free survival (chi(2) = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups.
For patients with LGNHL, first-line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination.
本研究的目的是比较三种治疗方案（单独使用克拉屈滨、克拉屈滨与环磷酰胺联合使用、或环磷酰胺、长春新碱和泼尼松联合使用）在既往未接受治疗的低度B细胞非霍奇金淋巴瘤（LGNHL）患者中的疗效。
在这项三臂、3期研究中，197例患者被随机分配接受6个疗程的单独克拉屈滨治疗、克拉屈滨与环磷酰胺联合治疗、或环磷酰胺、长春新碱和泼尼松联合治疗。对所有临床数据可获得的患者以及162例完成预定化疗的患者进行本研究终点分析。
与环磷酰胺、长春新碱和泼尼松联合治疗方案相比，单独使用克拉屈滨或克拉屈滨与环磷酰胺联合使用诱导更高的总体缓解概率（优势比[OR]=4.0；95%置信区间[CI]，1.7 - 9.3；P = 0.002，以及OR = 8.5；95%CI，3.2 - 22.7；P < 0.0001）、完全缓解（OR = 5.8；95%CI，1.8 - 18.5；P = 0.003；以及OR = 14；95%CI，4.4 - 44；P < 0.0001）、无进展生存期（对数秩检验P < 0.0001），但总生存期无差异。在多变量分析中纳入国际预后指数后，含克拉屈滨方案的治疗仍然是无进展生存期的独立预后因素（χ(2)=35.94；风险比 = 2.38；P < 0.0002）。随机分组组间感染发生率相似，而与环磷酰胺、长春新碱和泼尼松联合治疗相比，克拉屈滨与环磷酰胺联合使用（而非单独使用克拉屈滨）诱导更频繁的中性粒细胞减少、贫血和血小板减少（每项P < 0.05）。这导致克拉屈滨与环磷酰胺联合治疗和环磷酰胺、长春新碱和泼尼松联合治疗周期之间的间隔延长频率更高（P < 0.05），但单独使用克拉屈滨组、克拉屈滨与环磷酰胺联合治疗组以及环磷酰胺、长春新碱和泼尼松联合治疗组因血液学或其他毒性导致的剂量减少无显著差异。
对于LGNHL患者，一线单独使用克拉屈滨或克拉屈滨与环磷酰胺联合治疗方案均提供了相似的治疗反应、可接受的毒性，且比环磷酰胺、长春新碱和泼尼松联合治疗有更好的反应率。
