Hematology and Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
J Clin Oncol. 2011 Oct 20;29(30):3990-8. doi: 10.1200/JCO.2011.34.8508. Epub 2011 Sep 19.
Rituximab 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 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.
Three 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.
The 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.
利妥昔单抗联合环磷酰胺、多柔比星、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治疗方法之一。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。为了提高以无进展生存期（PFS）为主要终点的患者接受 R-CHOP 治疗的疗效，我们进行了一项 III 期研究。
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接受每 3 周（R-CHOP-21）或每 2 周（R-CHOP-14）一次的六周期 R-CHOP 联合 G-CSF。不允许维持性利妥昔单抗治疗。
300 例患者入组。在中位随访时间为 5.2 年时，对于 299 例合格患者，两个治疗组之间的 PFS 无显著差异；中位值分别为 R-CHOP-21 组 3.7 年和 R-CHOP-14 组 4.7 年，3 年时分别为 57%和 58%，6 年时分别为 41%和 43%（风险比 [HR]，0.92；95%CI，0.68 至 1.25；单侧 P =.30）。两个治疗组的中位总生存期（OS）均未达到，且无显著差异（6 年 OS：R-CHOP-21 组为 87%，R-CHOP-14 组为 88%；HR，1.15；95%CI，0.57 至 2.30；单侧 P =.65）。虽然 R-CHOP-21 组的 4 级中性粒细胞减少和 3 级感染更为常见，但 R-CHOP 在两个治疗组中均可行。
R-CHOP 剂量密集方案未能改善未经治疗的惰性 B 细胞淋巴瘤患者的 PFS。应探索进一步改善一线治疗或 R-CHOP 后缓解期治疗的方法。
