JCO:ABVD仍是进展期霍奇金淋巴瘤的标准治疗方案

2012-11-30 JCO JCO

        近日的一项研究表明,治疗进展期霍奇金淋巴瘤的Stanford V方案并没有超过ABVD方案(多柔比星+博来霉素+长春新碱+达卡巴嗪),相关的研究结果已在线发布于近期的临床肿瘤杂志(the Journal of Clinical Oncology,JCO)中。        &nb

        近日的一项研究表明,治疗进展期霍奇金淋巴瘤的Stanford V方案并没有超过ABVD方案(多柔比星+博来霉素+长春新碱+达卡巴嗪),相关的研究结果已在线发布于近期的临床肿瘤杂志(the Journal of Clinical Oncology,JCO)中。
 
 
        【研究背景】

        芝加哥西北大学(Northwestern University in Chicago)的Leo I. Gordon博士谈到,最近的随机临床试验表明治疗霍奇金淋巴瘤的诸多方案之间没有明显的差异。所以他认为目前主要应努力寻找影响霍奇金淋巴瘤预后的分子和免疫学标记,可选择的途径有基因表达谱、巨噬细胞标记和EB病毒等方法。

 
        【研究概览】

        东部合作肿瘤研究小组(Eastern Cooperative Oncology Group)、癌症和白血病研究B小组(the Cancer and Leukemia Group B)、西南肿瘤研究小组(Southwest Oncology Group)和加拿大NCIC临床试验小组(the Canadian NCIC Clinical Trials Group)的Gordon博士及其同事比较了794例进展期或局部扩展在接受或没有接受放疗的霍奇金淋巴瘤患者用12周Stanford V方案和6到8个疗程的ABVD治疗的结果。

        所有巨块纵隔肿块的患者在完成化疗后的2到3周接受放疗。此外,在Stanford V方案治疗组中所有治疗前肿块大于5cm和巨脾患者都接受36 Gy的的放疗。

        该研究报道了两个治疗方案的总反应率没有差异。ABVD方案和的Stanford V方案的完全缓解和临床完全缓解率分别为72.7%和68.7%。
经过中数6.4年的随访,将ABVD方案和Stanford V方案相比较,5年无障碍的生存率无明显差异(74% vs 71%);5年总生存率也无差异(均为88%)。

     伴局部进展的患者较III期和IV期患者好。高危患者经Stanford V方案治疗后的无障碍的生存率较经ABVD方案治疗后的无障碍的生存率长(分别为67%和57%;p=0.02)。

        尽管两个治疗组的药物毒性类似,Stanford V方案治疗组有更明显的3度淋巴细胞减少、3或4度白细胞减少、3和4度感觉神经病病变以及3或4度运动神经病变。

        ABVD方案组和Stanford V方案组的继发肿瘤的发生率相同,分别为15例和19例。

        Gordon博士总结到,尽管治疗进展期霍奇金淋巴瘤有多种方案,ABVD方案仍然标准的治疗方案。我们还没有BEACOPP方案与ABVD方案比较的大规模随机比对临床试验。当前的组间试验是将早期影像(PET)来预估治疗结果。但是没有一个随机比对临床试验。该试验利用早期影像(PET)来提供一些有用的信息。

        【研究评述】
    
        波士顿哈佛医学院(Harvard Medical School in Boston)的Dan L. Longo博士据此研究撰写了一篇评述。他谈到标准ABVD方案是霍奇金淋巴瘤患者的可选择方案。现在要搞清楚的是是否化疗6个疗程后需要加上放疗。

     评论进一步谈到,最佳的放疗用法还没有确定。一般地说,大多数患者不需接受放疗。如果患者在起病时就有大块的纵隔肿块,放疗是有益的,但是有继发肿瘤和早期冠脉疾病的危险。

        Longo博士还提到,新的药物正在出现,例如brentuximab vedotin。当它们的最佳使用方法确定后,就会进一步改善治疗效果。同时,如果选择ABVD方案应当尽可能避免放疗。

        评述进一步谈到,有理由期望下一个试验组将新药整合到霍奇金淋巴瘤的治疗中,这样可以将治愈率由85~90%提高到95~100%;同时减少后期的治疗相关毒性,这些治疗相关毒性可以影响的缩短被治愈患者的生存。



Purpose 
Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD.
Patients and Methods 
The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level.
Results 
There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32).
Conclusion 
ABVD remains the standard of care for patients with advanced Hodgkin lymphoma.

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    2013-04-06 yangfl06
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    2013-03-22 lidong40
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