Phase II/III Study of R-CHOP-21 Versus R-CHOP-14 for Untreated Indolent B-Cell Non-Hodgkin's Lymphoma: JCOG 0203 Trial
Phase II/III Study of R-CHOP-21 Versus R-CHOP-14 for Untreated Indolent B-Cell Non-Hodgkin's Lymphoma: JCOG 0203 Trial
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DOI：
10.1200/jco.2011.34.8508
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发表时间：
2011-10-20
影响因子：
45.3
通讯作者：
Hotta, Tomomitsu
中科院分区：
文献类型：
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作者：
Watanabe, Takashi;Tobinai, Kensei;Hotta, Tomomitsu
目的利妥昔单抗联合环磷酰胺、阿霉素、长春新碱和泼尼松 (R-CHOP) 是治疗惰性 B 细胞淋巴瘤最有效的一线疗法之一。粒细胞集落刺激因子 (G-CSF) 可增强抗体依赖性利妥昔单抗细胞毒性，用于缩短 CHOP 间隔。为了提高以 R-CHOP 治疗为主要终点的患者的无进展生存期 (PFS)，我们进行了一项 III 期研究。患者和方法未经治疗的 III 期至 IV 期惰性 B 细胞淋巴瘤患者被随机分配至 6 个周期的 R-CHOP 每 3 周 (R-CHOP-21) 或每 2 周 (R-CHOP-14) 联合 G-CSF。不允许维持利妥昔单抗。结果纳入300例患者。中位随访时间为 5.2 年，299 名符合条件的患者的 PFS 没有显着差异；中位数分别为 3.7 (R-CHOP-21) vs 4.7 (R-CHOP-14) 年，3 年时为 57% vs 58%，6 年时为 41% vs 43%（风险比 [HR]，0.92；95% CI，0.68 至 1.25；单侧 P = 0.30）。两组均未达到中位总生存 (OS) 时间，且无显着差异（6 年 OS：87% [R-CHOP-21] vs 88% [R-CHOP-14]；HR，1.15；95% CI，0.57 至 2.30；单侧 P = 0.65）。尽管 R-CHOP-21 组中 4 级中性粒细胞减少症和 3 级感染更常见，但 R-CHOP 在两组中都是可行的。 结论 R-CHOP 剂量密集策略未能改善未经治疗的惰性 B 细胞淋巴瘤患者的 PFS。应探索 R-CHOP 后一线治疗的进一步改进或缓解后治疗的研究。
PurposeRituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat indolent B-cell lymphoma. Granulocyte colony-stimulating factor (G-CSF), which potentiates antibody-dependent rituximab cytotoxicity, is used to shorten CHOP intervals. To improve progression-free survival (PFS) in patients treated with R-CHOP as the primary end point, we conducted a phase III study.Patients and MethodsPatients with untreated stages III to IV indolent B-cell lymphoma were randomly assigned to six cycles of R-CHOP every 3 weeks (R-CHOP-21) or every 2 weeks (R-CHOP-14) with G-CSF. Maintenance rituximab was not allowed.ResultsThree hundred patients were enrolled. At the median follow-up time of 5.2 years, there was no significant difference in PFS between arms for the 299 eligible patients; the median was 3.7 (R-CHOP-21) v 4.7 (R-CHOP-14) years, 57% v 58% at 3 years, and 41% v 43% at 6 years, respectively (hazard ratio [HR], 0.92; 95% CI, 0.68 to 1.25; one-sided P = .30). The median overall survival (OS) time was not reached in either arm, and there was no significant difference (6-year OS: 87% [R-CHOP-21] v 88% [R-CHOP-14]; HR, 1.15; 95% CI, 0.57 to 2.30; one-sided P = .65). Although grade 4 neutropenia and grade 3 infections were more frequent in the R-CHOP-21 group, R-CHOP was feasible in both arms.ConclusionThe R-CHOP dose-dense strategy failed to improve PFS of patients with untreated indolent B-cell lymphoma. Further improvement of first-line treatment or investigations on postremission therapy following R-CHOP should be explored.