编者按:ABVD是经典型霍奇金淋巴瘤(HL)的一线治疗方案,欧洲研究认为BEACOPP在预后不良的患者中疗效更好。然而,近期EORTC 20012研究得出了阴性的结果。该如何评价这两种一线方案?目前是否还有其他化疗方案有望撼动ABVD方案在HL治疗中的“统治地位”?抱着上述疑问,小编在不久前结束的2016欧洲血液学协会(EHA)年会上特邀请克罗地亚萨格勒布大学医院中心I Aurer教授进行了专访,请他分享了关于HL治疗最新进展的独到见解。现将其内容整理成文,以飨读者。
克罗地亚萨格勒布大学医院中心I Aurer教授访谈
《肿瘤瞭望》:霍奇金淋巴瘤一线治疗方案以ABVD和BEACOPP为主,您认为在两者之间应如何取舍?BEACOPP是否可以取代ABVD方案成为霍奇金淋巴瘤一线治疗的经典?
Aurer教授:目前,霍奇金淋巴瘤一线方案的选择仍是个悬而未决的问题。诚如你所说,BEACOPP效果比ABVD更好,但同时也带来了更显著的毒副作用。统一的BEACOPP将使所有患者暴露于更高的不良反应风险当中,而其中可能仅有5-%~10%的患者获得收益。这种取舍是否合理,因此专家们对此持有不同的意见。从我个人角度来讲,我更赞成BEACOPP增强方案,ABVD的地位并不是不可撼动的。当然,这仅是一家之言。
Dr. Aurer: Well, the question of the choice of the frontline therapy in Hodgkin lymphoma is an unanswered question—I think it’s unanswerable. Because escalated BEACOPP, as you said, is definitely more effective. However, it’s also significantly more toxic. And it’s a matter of opinion whether you think it’s worthwhile exposing 100 percent of patients to increased toxicity in order to help the outcome of 5 to 10 percent. Personally, I am a fan of escalated BEACOPPand I would not agree with the statement that ABVD is unshakeable. But as I said, this is really a matter of opinion.
《肿瘤瞭望》:霍奇金淋巴瘤的二线治疗方案有很多选择,您认为是什么限制了不同挽救治疗方案间的对比研究,以及我们如何解决这个问题。
Aurer教授:霍奇金淋巴瘤二线治疗的情况与侵袭性淋巴瘤的治疗很相似:似乎多种方案都能取得类似的效果。因此,如何取舍取决于当地医疗机构的经验及具体情况。通常情况下,临床医师应根据患者的合并症情况选择药物,例如合并有肾脏病变的患者需要尽量避免肾毒性药物的应用。多种方案的效果相似,这仅是一种现象,而我们不需要强行要求统一方案。
Dr. Aurer:Well, the situation in Hodgkin lymphoma second line cell therapy is very similar to what we see in aggressive lymphomas. It seems that a number of different chemotherapy regimens can achieve the same result. And therefore, which one you use is really dependent on the local experience and practice. Maybe, in some instances, you can pick up the protocol depending on the toxicity that you want to avoid in patients, for instance, whether renal toxicity should be avoided (or something like that). So, it’s simply a fact that all of these regimens produce very, very similar effects—and that is a fact.
《肿瘤瞭望》:您的团队今年发表了一项研究,结果显示大剂量异环磷酰胺联合米托蒽醌(HDIM)安全有效。您能给我们简单介绍一下这项化疗方案的渊源,以及您认为其相比较于目前的MINE、ICE以及包含阿糖胞苷的方案有何优劣吗?
Aurer教授:我认为HDIM与ICE、DHAP及MINE-ESHAP方案效果等同,目前并没有确切证据显示某一种方案比其他具有更显著的优势。如何取舍取决于我前面所提到的,患者的具体情况。我们在HDIM应用方面已经累积了超过10年的经验,前期试验证实我们的患者队列对HDIM反应良好,因此我们认为HDIM方案有可能有较好的疗效,且不良反应较少。总之,关于HDIM治疗霍奇金淋巴瘤的这项长达10年的研究,其结果符合我们的预期,HDIM被证实是安全有效的。
Dr. Aurer: Well, I thinka high-dose ofifosfamide and mitoxantroneaged in protocol produces results that are practically identical to that of ICE, DHAP, or MINE-ESHAP,whatever. So I don’t think there are any substantial advantages or disadvantages to any of these protocols. So they can be used depending on, again, whether you want to avoid cisplatin or other things like that. So how did HDIM evolve? Well, it’s a long story, actually. More than 10 years ago, we did a study using this regimenas amodelization regimen and we had some very good results in a few hodgkin lymphoma patients that were included.And we, therefore, just continued using it because we’re familiar with that and felt that it has good efficacy and acceptable toxicity. And we now have the chance to analyze our results and publish it, which proves our first impression that it’s effective and acceptably toxic.
《肿瘤瞭望》:PD-1抑制剂在霍奇金淋巴瘤治疗中显示出独特的优势,其耐受性及安全性良好。然而,联合其他药物有可能增加毒副反应。这是否意味着目前我们只能将其应用于单药治疗,或者您认为还有那些联合方案更具有优势?
Aurer教授:PD-1抑制剂是一类颇具发展前景的新药。单药应用毒副作用较小,与放疗联合可以增强后者的疗效,很有可能还可以增强化疗的效果。至于单药还是联合应用目前还在研究阶段,评价这类药物的地位也还为时尚早。
Dr. Aurer: Regarding the PD-1 inhibitors—this is a group of very interesting and very promising agents. If you use this monotherapy, their toxicity seems to be minor, and they seem to increase the efficacy of radiation therapy (and possibly chemotherapy). So whether they will finally be used as monotherapy or in combination remains to be seen. Studies need to be done and it is, I think, much too early to speculate on what will be their place and how they will be used.
《肿瘤瞭望》:NCCN也建议应用低剂量CT和MRI密切监测二次肿瘤的发生。您认为现在是否是探索减低毒性化疗的最好时机?
Aurer教授:二次肿瘤是摆在肿瘤患者长期生存面前的一个重要问题。然而我们必须谨记,在考虑二次肿瘤的问题之前,患者必须获得初发肿瘤的缓解。个人非常反对减低剂量化疗,减低剂量很可能以损失疗效为代价,从而导致患者在生存期方面的不必要损失。我们已经在减小放疗范围、减少烷化剂应用方面取得诸多进展,二次肿瘤的问题得到了一定的阻遏。但问题在于,我们现在采取措施,有可能10年甚至20年后才能看到结果,为此我们需要等待相当长一段时间。在此期间,盲目减低剂量化疗并不可取。另一方面,据我所知,欧洲多数国家并不采用NCCN的建议,应用CT或者MRI来监测二次肿瘤发生。我们常规进行的是乳腺影像学检查,尤其对那些接受纵膈放疗的女性患者,定期进行X线、超声或者MRI筛查,同时也会进行一些涉及甲状腺的筛查。
Dr. Aurer:The second cancer problem is a big problem in cancer survivors; however, one should keep in mind that in order to have a second cancer, you have to survive your first cancer. So, I am very much against reducing treatment that might lead to reduced efficacy in treating first cancers. We have had improvements there also, with the reduction in size of radiation fields, and with the use of chemotherapy that contains less alkylating agents, we are seeing less second cancers than we used to earlier. The problem is that what we do now, we’ll see have its effect in 10, 15, 20 years. So we need to wait a lot to see what changes will be brought about by the changes in our practice. As far as I know, the Europeans do not share the recommendations of NCCN to do checks ups with CT scans or MRIs to detect early cancer. What is done in regular practice is breast imaging, be it mammography or ultrasound or magnetic resonance in women that have been treated for cancer, especially if they had mediastinal radiation,and we also screen for thyroid cancer with ultrasound and things like that.