R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial
R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial
复制标题
DOI：
10.1002/hon.2524
复制
发表时间：
2018-10-01
影响因子：
3.3
通讯作者：
Tsurumi, Hisashi
中科院分区：
文献类型：
--
作者：
Hara, Takeshi;Yoshikawa, Takeshi;Tsurumi, Hisashi
吡柔比星(简称四氢吡喃阿霉素[THP])是一种比阿霉素(DOX)心脏毒性小的蒽环类药物。我们先前在2期研究中报道了由利妥昔单抗(R)、THP、环磷酰胺(CPA)、长春新碱(VCR)和强的松龙(PSL)组成的R-THP-COP治疗弥漫性大B细胞淋巴瘤(DLBCL)的疗效和安全性。在这里，我们前瞻性地比较了R-THP-COP方案和标准R-CHOP方案(由R、CPA、DOX、VCR和PSL组成)的有效性和安全性。这项前瞻性、随机化的3期研究纳入了年龄在70岁以下、以前未接受治疗的DLBCL患者。方案包括R(第1天)、DOX或THP(第3天)、CPA(第3天)、VCR(第3天)和PSL，每3周5天，共6~8个周期。2006年7月5日至2013年6月11日，81例患者随机分为治疗组(R-CHOP组，40例；R-THP-COP组，41例)。以完全缓解率为主要终点评价，R-THP-COP疗效不逊于R-CHOP(分别为85%和85%)。中位随访期75.2个月，R-CHOP组和R-THP-COP组的5年总生存率分别为87%和82%(危险比[HR]：0.89，95%可信区间[CI]：0.31~2.49；P=.82)。R-CHOP组和R-THP-COP组的5年无进展生存率分别为74%和79%(HR：1.37，95%CI：0.56~3.55；P=0.49)。两组均未观察到3级心脏副作用。除R-THP-COP组与治疗相关的急性髓系白血病外，两组均未观察到严重的晚期不良反应。这些数据表明，R-THP-COP在临床疗效方面不逊于R-CHOP，且具有可接受的安全性。因此，该方案可能是R-CHOP的一种替代疗法。
Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5days every 3weeks for 6 to 8cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P=.82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P=.49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP.