末期何杰金氏淋巴瘤标准照护的挑战

　　December 12, 2006 — 研究者在美国血液学会第49届年会和展览中表示，一篇德国研究的十年结果，支持使用逐渐增强的化疗处方作为末期何杰金氏淋巴瘤(advanced-stage Hodgkin's lymphoma)的第一线治疗，这挑战了现有的照护标准。
　　
　　这些最新资料来自德国的何杰金研究小组，由科隆大学的Volker Diehl医师于会中发表，结果显示，一种渐强式的BEACOPP处方(包括bleomycin、etoposide、doxorubicin、cyclophosphamide、vincristine、procarbazine以及 prednisone)的结果更优；相较于标准照护处方，该处方18%有更好的肿瘤控制(无治疗失败或者无恶化存活)，11%有更好的整体存活；标准处方如COPP(cyclophosphamide、vincristine、procarbazine以及prednisone)或者ABVD(doxorubicin、bleomycin、vinblastin以及dacarbazine)。
　　
　　Diehl医师解释，他的团队先回顾1992年的集中式处方，因为当时没有新药，而标准化疗处方的成功率约为70%，他表示，我们认为应该可以更好。
　　
　　该研究包括1,196位病患，随机分派接受渐强式BEACOPP (n=466)、基础 BEACOPP处方 (n=469)或者标准照护COPP/ABDV处方(n=261)；COPP/ABDV组的病患较少，因为它在显示出比其他两组不优时被提前结束(在三年后)。
　　
　　【10年存活率】

	COPP/ABVD (%)	基础BEACOPP (%)	渐强式 BEACOPP (%)
未治疗失败	64	70	82
整体存活	75	80	86

　　Diehl向与会听众表示，渐强式BEACOPP处方的两种结果都较优，本处方的长期和急性毒性也较多，但是因为急性毒性的死亡率并非最高；COPP/ABDV组的十年死亡率是11.8%，渐强式BEACOPP组是2.8%，这表示标准照护组病患的死亡风险是四倍。
　　
　　该段会议的主持人，芝加哥大学的Sonali Smith医师向Medscape肿瘤学表示，这是一个重要的研究，其研究团队在2003年曾于新英格兰医学期刊（New England Journal of Medicine(348:2386-2395) ）发表过五年的结果，这些更新的资料显示，渐强式BEACOPP显然更优；该处方在美国渐渐普及，然而尚未获得更广泛的支持，这些新的资料让我们停下来想想，现在可以考虑使用此一处方了。
　　
　　Smith医师指出，绝大多数的美国医师使用ABVD处方，因为该处方自1990年来有第三期试验资料作为证据，而且耐受良好、方便给药；有些顾虑认为渐强式BEACOPP处方比较有毒性，也有顾虑次发急性骨髓性白血病(secondary acute myeloid leukemia，AML)之风险；在Diehl医师发表的结果中，渐强式BEACOPP组有14位病患发生AML，主要是因为etoposide药物所致，COPP/ABDV组有1 位，基础BEACOPP组有7位；不过，尽管如此，渐强式BEACOPP组的整体存活率还是较优。
　　
　　Diehl医师在会中表示，目前有三个有关渐强式BEACOPP的随机前溯试验，纳入2,500位以上病患，整体观之，AML的发生率只有0.8%；他也指出，虽然渐强式BEACOPP处方的血液毒性增加，并不会导致更早死亡，而试验中三组病患的次发恶性病的比率相似。
　　
　　他也指出，正子断层造影(PET)扫描渐渐被用于评估何杰金氏淋巴瘤的预后，未来的策略之一是，PET阴性的病患使用标准ABDV处方，PET阳性的病患使用渐强式BEACOPP处方。
　　
　　Diehl医师报告接受Johnson & Johnson, Amgen以及 Chugai等之研究基金。
　　
　　美国血液学会第49届年会和展览：摘要 211。发表于2007年12月10日。

 

Challenge to Standard Care in Advanced-Stage Hodgkin's Lymphoma

By Zosia Chustecka
Medscape Medical News

 

December 12, 2006 — Ten-year results from a German study support the use of an escalated chemotherapy regimen for the first-line treatment of advanced-stage Hodgkin's lymphoma and challenge the current standard of care, researchers told the American Society of Hematology 49th Annual Meeting in Atlanta, Georgia.

The updated data from the German Hodgkin Study Group were presented at the meeting by Volker Diehl, MD, from the University of Cologne, Germany. The results showed superior outcomes with a regimen known as escalated BEACOPP, comprising bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. This regimen gave 18% better tumor control (freedom from treatment failure or progression-free survival) and 11% better overall survival than a standard-care regimen, which was COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin and dacarbazine), he said.

Dr. Diehl explained that his group set out to study the intensive regimen back in 1992 because there were no new drugs on the horizon, and the standard chemotherapy regimens had a success rate of about 70%. "We thought that we could do better than that," he said.

The study involved 1196 patients randomized to receive escalated BEACOPP (n = 466), a baseline BEACOPP regimen (n = 469), or the standard-of-care COPP/ABDV regimen (n = 261). The COPP/ABDV group had fewer patients because it was closed prematurely (after 3 years) when it was shown to be inferior to the other 2 groups.

Survival Rates at 10 Years

	COPP/ABVD	Baseline BEACOPP	Escalated BEACOPP
Freedom from treatment failure	64%	70%	82%
Overall survival	75%	80%	86%

The escalated BEACOPP regimen was superior in both outcomes, Dr. Diehl told the meeting. "There is more toxicity with this regimen, both long-term and acute, but the death rate due to acute toxicity was not higher," he said. "The death rate over 10 years was 11.8% in the COPP/ABDV arm and 2.8% in the escalated BEACOPP arm, which means about 4 times more patients have died in the standard arm."

"This is an important study," Sonali Smith, MD, from the University of Chicago, Illinois, and session moderator, commented to Medscape Oncology. Earlier 5-year results from this group were reported in the New England Journal of Medicine in 2003 (348:2386-2395), she noted, and these updated data show very clearly that the escalated BEACOPP regimen is superior. This is a regimen that is gaining popularity in the United States, although it has not gained widespread support, she commented. "These new data give us pause for thought, so that now we should consider using it," Dr. Smith commented.

"The overwhelming majority of US physicians use the ABVD regimen because it is well proven, supported by phase 3 data from the 1990s, and it is well tolerated and easy to administer," Dr. Smith added. There has been some concern that the escalated BEACOPP regimen is more toxic, and there has been concern about the risk for secondary acute myeloid leukemia (AML), she said. In the results Dr. Diehl presented, there were 14 patients with AML in the escalated BEACOPP group, which he attributed mainly to etoposide, 1 patient in the COPP/ABDV group, and 7 patients in the baseline BEACOPP group. "However, despite this, the overall survival was superior with the escalated BEACOPP regimen," Dr. Smith pointed out.

Dr. Diehl told the meeting that there have now been 3 randomized prospective trials with escalated BEACOPP involving more than 2500 patients and, overall, these show a rate of AML of only 0.8%. He also commented that although there was some increased hematological toxicity seen with the escalated BEACOPP regimen, it did not lead to early mortality, and the rates of secondary malignancy were similar in all 3 groups of the trial.

He also mentioned that positron emission tomography (PET) scanning is increasingly being used to assess the prognosis for Hodgkin's lymphoma, and 1 strategy for the future would be to use the standard ABDV regimen in patients who are PET-negative, but to go with the escalated BEACOPP regimen in patients who are PET-positive.

Dr. Diehl reports receiving research funding from Johnson & Johnson, Amgen, and Chugai.

American Society of Hematology (ASH) 49th Annual Meeting and Exposition: Abstract 211. Presented December 10, 2007.