ORLANDO (EGMN) – An aggressive approach to treating early unfavorable Hodgkin’s lymphoma that combines the BEACOPP regimen at an escalated dose with the ABVD regimen and involved-field radiotherapy results in better tumor control than did ABVD and radiation alone, investigators have reported.

In the final analysis of the German Hodgkin Study Group (GHSG) HD14 trial, the estimated 5-year freedom-from-treatment-failure rate among patients treated with escalated-dose BEACOPP and ABVD plus radiotherapy (RT) was 94.3%, compared with 87.6% for those treated with ABVD/RT alone. The hazard ratio for BEACOPP/ABVD/RT was 0.49 (P =.0001), Dr. Peter Borchmann said at the annual meeting of the American Society of Hematology.

“We have this new treatment as the new standard of care at least in our studies. It will be challenged here in the U.S., because many doctors in the U.S., I guess, will still say ‘ABVD is the standard of care, and we don’t care about some 7% better tumor control at 5 years; we want to see overall survival differences.’ With this short follow-up we have now, there is no difference in overall survival,” lead author Dr. Andreas Engert from University Hospital Cologne, Germany, said in a media briefing.

Although BEACOPP is associated with an increased risk for infertility, 18% of women up to age 40 years who were treated with the regimen reported having a pregnancy or giving birth more than 1 year after the end of therapy, compared with 11% treated with ABVD. Dr. Borchmann, also of University Hospital Cologne, said that all the women were able to conceive using their own eggs.

The GHSG HD14 trial compared four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD. In both treatment groups, chemotherapy was followed by involved field radiotherapy (IF-RT) at a dose of 30 Gy.

The patients had stage I or II disease with early unfavorable risk factors, including at least three involved lymph node areas, elevated erythrocyte sedimentation rate, large mediastinal mass, or extranodal disease. They were randomly assigned to either ABVD plus IF-RT in the control arm (818 patients) or BEACOPP/ABVD plus IF-RT in the experimental arm (805 patients). Patients were recruited from cancer centers and smaller oncology practices in Germany, Austria, Switzerland, the Czech Republic, and the Netherlands.

In July of 2008, the control arm was closed following an interim analysis that showed that the experimental arm had met the prespecified criteria for superiority.

An intention-to-treat analysis showed that both regimens had excellent tumor control, with 93.8% of patients in the control arm having complete responses (CR) or complete responses unconfirmed (CRu), compared with 94.5% of patients in the BEACOPP/ABVD arm. A total of 1.2% of patients in the control arm had partial responses, compared with 0.5% in the BEACOPP/ABVD arm. Relapses occurred in 8.1% and 2.6% of patients in the two arms, respectively.

Acute toxicities of either grade III or IV according to World Health Organization criteria occurred in 51% of patients on ABVD alone, and 87% of patients in the combination arm. Hematologic toxicities occurred in 24% and 80% and leukopenia with infections occurred in 1.2% and 9.8%, respectively.

In addition, there were no cases of acute myeloid leukemia or myelodysplasia among control patients, compared with three (0.4%) patients treated with BEACOPP/ABVD. Conversely, there were 10 cases of non-Hodgkin’s lymphoma (1.2%) among patients on ABVD alone, vs. 5 (0.6%) in those on BEACOPP/ABVD. Solid tumors occurred in nine (1.1%) and eight (1.0%) patients, respectively.

There were 20 deaths in each treatment arm. In the control arm, there were no deaths attributed to the study regimen and six deaths related to toxicity of the salvage regimen, compared with four and one, respectively, in the BEACOPP/ABVD arm. Secondary neoplasms were the cause of death in seven patients on ABVD alone, and three on BEACOPP/ABVD.

“I think it’s very reasonable to say that this regimen [BEACOPP/ABVD] regimen will become the new standard treatment for early unfavorable Hodgkin lymphoma patients. And I think this is a very strong chemotherapy background for the much more important question we are asking all over the world right now: Do we need combined modality treatment for these patients, or can we restrict radiotherapy to a subset of patients [with PET-positive residual disease],” Dr. Borchmann concluded.

The trial was supported by the German Cancer Aid fund. Dr. Borchmann and Dr. Engert had no conflict of interest disclosures.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

奥兰多(EGMN)——研究者称，一种积极治疗早期恶性霍奇金淋巴瘤的组合疗法正在被采用，这种疗法将ABVD疗法、涉及区域放射治疗和剂量递增的BEACOPP疗法相结合，比单独采用ABVD和放射治疗更能控制肿瘤。 

德国霍奇金病研究小组(GHSG)的HD14小组研究选取的受试者为存在第一或第二阶段该症的早期恶性风险因素的患者，其中包括至少三块以上淋巴结区域、红细胞沉降率升高、纵膈腔空间增大和结外疾病，这些患者招募自德国、奥地利、瑞士、捷克共和国和荷兰的多个肿瘤中心和小型肿瘤诊所。研究者将其随机分配到ABVD加IF-RT治疗对照组(818名患者)或BEACOPP/ABVD加IF-RT联合治疗组(805名患者)，并比较四周期的ABVD治疗(分别使用阿霉素、博莱霉素、长春新碱和达卡巴嗪进行治疗)与剂量递增的BEACOPP治疗方法(分别使用博莱霉素、依托泊苷、阿霉素、环磷酰胺、长春新碱、甲基苄肼、强的松进行治疗)。这两种化疗后都使用了30 Gy的涉及区域放射治疗(IF-RT)。 

2008年7月，中期分析表明联合治疗组的已经达到优势的特定标准后，对照组亦结束治疗。意向处理分析表明，两种治疗方案对于肿瘤都控制良好，对照组中93.8%的患者已完全反应(CR)，或不确定地完全反应(CRu)，而BEACOPP/ABVD治疗组为94.5%。对照组中总共有1.2%的患者有部分反应，而BEACOPP/ABVD治疗组为0.5%。这两组的复发率分别为8.1%和2.6%。与单独使用ABVD/RT治疗的患者5年无治疗失败生存率87.6%相比，通过递增剂量BEACOPP和ABVD放射治疗结合治疗的患者该指标为94.3%。组合疗法的危险比为0.49(P=0.0001)。 

根据世界卫生组织规定的三级或四级标准，ABVD单独治疗时患者急性毒性发生率为51%，组合疗法组为87%。血液毒性发生率分别为24%和80%，感染引起的白细胞减少症发生率分别为1.2%和9.8%。此外，对照组患者未发生急性髓细胞性白血病或骨髓发育不良，而BEACOPP/ABVD组合疗法组发生3例(发生率为0.4%)。相反，ABVD单独治疗组发生10例非霍奇金淋巴瘤(发生率为1.2%)，而BEACOPP/ABVD组合疗法组发生5例(发生率为0.6%)。实体瘤分别发生9例和8例，发生率分别为1.1%和1.0%。每种治疗组均有20例死亡病例。对照组中，未见因研究方案相关的死亡病例，其中有6例是因为抢救方案的毒性而致死，而组合疗法组分别为4例研究方案相关死亡病例，其中1例是因为抢救方案的毒性而致死。ABVD单独治疗组中，有7例患者是因为继发性肿瘤而致死，而BEACOPP/ABVD组合疗法组中有3例。 

本研究得到德国肿瘤研究基金资助。研究者无其他披露内容。 

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