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早期预后不良或晚期霍奇金淋巴瘤患者中,强化BEACOPP化疗方案与ABVD化疗方案的比较。

Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma.

作者信息

Bauer Kathrin, Skoetz Nicole, Monsef Ina, Engert Andreas, Brillant Corinne

机构信息

Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, Cologne, Germany, 50924.

出版信息

Cochrane Database Syst Rev. 2011 Aug 10(8):CD007941. doi: 10.1002/14651858.CD007941.pub2.

Abstract

BACKGROUND

There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen.

OBJECTIVES

To provide an evidence-based answer regarding the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD.

SEARCH STRATEGY

We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to November 2010) and EMBASE (1985 to November 2008).

SELECTION CRITERIA

We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared to chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL.

DATA COLLECTION AND ANALYSIS

Effect measures used were hazard ratios (HR) for overall survival (OS), progression-free survival (PFS) and freedom from first progression. Relative risks were used to analyse complete response rate, treatment-related mortality and adverse events. Two independent review authors extracted data and assessed quality of trials.

MAIN RESULTS

A total of 790 records were screened. Five eligible trials (four published, one ongoing), were identified. These trials included only adult patients (16 to 60 years of age). Four trials with 2868 patients were included in the meta-analyses: the HD9 and HD14 trials from Germany, the HD2000 and GSM-HD trials from Italy. All trials reported results for PFS and OS. PFS was statistically significantly longer for escalated BEACOPP: HR was 0.53 (95% confidence interval (CI) 0.44 to 0.64, I(2) = 0%). There was no statistically significant difference in OS between the comparators: HR was 0.80 (95% CI 0.59 to 1.09, I(2) = 0%). Three trials reported adverse events: the escalated BEACOPP regimens caused statistically significantly more haematological toxicities WHO grade III or IV (anaemia P < 0.00001, neutropenia P = 0.007, thrombocytopenia P < 0.00001), infections (P < 0.00001)) and occurrence of myeloid dysplastic syndrome (MDS) or acute myeloid leukemia (AML) (P = 0.05). There were no differences between both regimens for secondary malignancies, treatment-related mortality or infertility.

AUTHORS' CONCLUSIONS: This meta-analysis showed that adult patients between 16 and 60 years of age with early unfavourable or advanced stage HL benefited from chemotherapy including escalated BEACOPP regarding PFS, but there was no significant difference in OS. Longer follow-up and the inclusion of the EORTC 20012 trial will lead to a more definitive answer with respect to OS.

摘要

背景

对于早期预后不良和晚期霍奇金淋巴瘤(HL)的治疗,存在两种不同的国际标准:采用强化BEACOPP(博来霉素/依托泊苷/阿霉素/环磷酰胺/长春新碱/丙卡巴肼/泼尼松)方案进行化疗,以及采用ABVD(阿霉素/博来霉素/长春花碱/达卡巴嗪)方案进行化疗。

目的

提供基于证据的答案,以说明与包含ABVD的化疗相比,包含强化BEACOPP的化疗的优缺点。

检索策略

我们在MEDLINE、CENTRAL和会议论文集(1985年1月至2010年11月)以及EMBASE(1985年至2008年11月)中检索随机对照试验。

选择标准

我们纳入了随机对照试验,这些试验比较了作为早期预后不良或晚期HL患者一线治疗的包含至少两个周期强化BEACOPP方案的化疗与包含至少四个周期ABVD方案的化疗。

数据收集与分析

使用的效应测量指标为总生存期(OS)、无进展生存期(PFS)和首次进展时间的风险比(HR)。相对风险用于分析完全缓解率、治疗相关死亡率和不良事件。两名独立的综述作者提取数据并评估试验质量。

主要结果

共筛选了790条记录。确定了5项符合条件的试验(4项已发表,1项正在进行)。这些试验仅纳入成年患者(16至60岁)。四项试验共2868例患者被纳入荟萃分析:德国的HD9和HD14试验、意大利的HD2000和GSM-HD试验。所有试验均报告了PFS和OS的结果。强化BEACOPP方案的PFS在统计学上显著更长:HR为0.53(95%置信区间(CI)0.44至0.64,I² = 0%)。比较组之间的OS无统计学显著差异:HR为0.80(95%CI 0.59至1.09,I² = 0%)。三项试验报告了不良事件:强化BEACOPP方案导致的血液学毒性(WHO III级或IV级)在统计学上显著更多(贫血P < 0.00001,中性粒细胞减少P = 0.007,血小板减少P < 0.00001)、感染(P < 0.00001)以及骨髓增生异常综合征(MDS)或急性髓细胞白血病(AML)的发生(P = 0.05)。两种方案在继发性恶性肿瘤、治疗相关死亡率或不育方面无差异。

作者结论

这项荟萃分析表明,16至60岁的早期预后不良或晚期HL成年患者在PFS方面从包含强化BEACOPP的化疗中获益,但OS无显著差异。更长时间的随访以及纳入EORTC 20012试验将对OS得出更明确的答案。

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