Randomised Comparison of the Stanford V (SV) Regimen and ABVD in the Treatment of Advanced Hodgkin Lymphoma (HL): Results from a UK NCRI Lymphoma Group Study, ISRCTN 64141244
Randomised Comparison of the Stanford V (SV) Regimen and ABVD in the Treatment of Advanced Hodgkin Lymphoma (HL): Results from a UK NCRI Lymphoma Group Study, ISRCTN 64141244
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斯坦福 V (SV) 方案和 ABVD 治疗晚期霍奇金淋巴瘤 (HL) 的随机比较：英国 NCRI 淋巴瘤组研究的结果，ISRCTN 64141244
DOI：
10.1182/blood.v112.11.370.370
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发表时间：
2008
期刊：
影响因子：
20.3
通讯作者：
P. Hoskin
中科院分区：
文献类型：
--
作者：
P. Johnson;A. Horwich;A. Jack;G. Mead;B. Hancock;Paul D. Smith;W. Qian;P. Patrick;A. Pettitt;Dennis Cunningham;P. Hoskin
引言：将每周交替SV方案与标准ABVD方案进行比较。进行了初始随机化II期初步研究以确定耐受性和应答率，随后将研究扩展为III期试验。研究方法：晚期HL（大块病变、B症状和/或III/IV期）的初治患者（pts）随机分为6 - 8个周期的ABVD或12周的SV，两组均接受初始大块病变（> 5 cm）或脾脏沉积部位和残留肿块的受累野照射（34 - 36 Gy）。在III期研究中，达到完全缓解的ABVD患者不需要放疗。给予的药物为：ABVD（第1天和第15天）：多柔比星25 mg/m2、博莱霉素10000 iu/m2、长春碱6 mg/m2、达卡巴嗪375 mg/m2），q28。SV（莫司汀6mg/m2，第1、5、9周，多柔比星25mg/m2，第1、3、5、7、9、11周，长春碱6mg/m2，第1、3、5、7、9、11周，泼尼松40mg/m2，隔日给药，长春新碱1.4mg/m2，第2、4、6、8、10、12周，博莱霉素5000iu/m2，第2、4、6、8、10、12周，依托泊苷60 mg/m2，连续2天（第3、7、11周）。主要结局指标为无进展生存期（PFS）。总共需要97起事件才能检测到5年PFS的改善，从ABVD的75%改善到SV的85%，显着性水平为5%，把握度为80%。结果：520例患者在1998年3月至2006年10月期间接受随机化（261例ABVD，259例SV）。平均年龄为35岁。49%的患者为I/II期疾病伴大量和/或B症状，29%为III期，22%为IV期。总体上74%的患者有B症状，52%的患者有本体疾病。国际预后评分（IPS）显示37% 0 - 1，54% 2 - 3和9% 4 - 7。治疗组的基线预后因素匹配良好。95%的SV患者完成了12周治疗，94%的ABVD患者完成了6（71%）或7/8（23%）个周期治疗。37例患者（27例ABVD，10例SV）报告了III/IV级肺毒性。SV（19%）报告的非肺部III/IV级毒性多于ABVD（8%）。总体上62%的患者接受了放疗：72%的SV和53%的ABVD。完成所有治疗时，SV和ABVD的总缓解率（CR、CRu、PR）分别为90%和89%。ABVD组有1例因毒性死亡，SV组无。中位随访时间为4年，113例患者（ABVD组55例，SV组58例）疾病复发或死亡，风险比为1.10（95% CI = 0.76，1.59; p = 0.61），ABVD组5年PFS为76%，SV组为74%，绝对差异2%（95% CI = − 5%，11%）。40例患者死亡（ABVD组22例，SV组18例），风险比为0.81（95% CI = 0.44，1.52; p = 0.51），ABVD组5年总生存率（OS）为90%，SV组为92%，绝对差异2%（95% CI-5%，5%）。根据分期或IPS，预先计划的亚组分析未显示这些结果的显著差异。结论：在这项广泛使用巩固放疗并包括相对有利队列的试验中，没有证据表明SV和ABVD之间的PFS和OS存在差异。ABVD组报告的肺毒性更多，而SV组的其他毒性略高。
Introduction: The weekly alternating SV regimen was compared to standard ABVD. An initial randomised phase II pilot study was carried out to determine tolerability and response rate, following which the study was expanded into a phase III trial. Methods: Consenting patients (pts) with advanced HL (bulk disease, B symptoms and/or stage III/IV) were randomised between 6–8 cycles of ABVD or 12 weeks SV, to be followed in both arms by involved field irradiation (34–36Gy) to sites of initial bulk disease (>5cm) or splenic deposits, and to residual masses. In the phase III study radiotherapy was not required for ABVD pts who achieved complete remission. Drugs given were: ABVD (days 1 & 15): doxorubicin 25mg/m2, bleomycin 10000iu/m2, vinblastine 6mg/m2, dacarbazine 375mg/m2), q28. SV (mustine 6mg/m2, wks 1,5,9, doxorubicin 25mg/m2, wks 1,3,5,7,9,11, vinblastine 6mg/m2 wks 1,3,5,7,9,11, prednisone 40mg/m2 alternate days, vincristine 1.4mg/m2 wks 2,4,6,8,10,12, bleomycin 5000iu/m2 wks 2,4,6,8,10, 12, etoposide 60 mg/m2, 2 consecutive days wks 3,7,11). The primary outcome measure was progression-free survival (PFS). A total of 97 events were required to detect an improvement in 5-year PFS from 75% in ABVD to 85% in SV with a 5% significance level and 80% power. Results: 520 pts were randomized (261 ABVD, 259 SV) between 3/98 and 10/06. Median age was 35. 49% had stage I/II disease with bulk and/or B symptoms, 29% stage III, 22% stage IV. 74% of pts overall had B symptoms and 52% bulk disease. International Prognostic Score (IPS) showed 37% 0–1, 54% 2–3 and 9% 4–7. The treatment groups were well matched for baseline prognostic factors. 95% SV pts completed 12 weeks, and 94% ABVD had 6 (71%) or 7/8 (23%) cycles. Pulmonary toxicity grade III/IV was reported in 37 pts (27 ABVD, 10 SV). More non-pulmonary grade III/IV toxicities were reported in SV(19%) than in ABVD (8%). Radiotherapy was given in 62% overall: 72% SV and 53% ABVD. The overall response rate (CR, CRu, PR) at completion of all treatment was 90% for SV and 89% for ABVD. There was one death due to toxicity on the ABVD arm, and none in SV. With a median 4 years follow up, 113 pts (55 ABVD, 58 SV) had recurrent disease or died with a hazard ratio of 1.10 (95% CI =0.76, 1.59; p=0.61) and 5-year PFS of 76% in ABVD and 74% in SV, absolute difference 2% (95% CI= −5%, 11%). 40 pts died (22 ABVD, 18 SV) with a hazard ratio of 0.81 (95% CI=0.44, 1,52; p=0.51) and 5-year overall survival (OS) of 90% in ABVD and 92% in SV, absolute difference 2% (95% CI -5%, 5%). Pre-planned analysis of sub-groups did not show significant variation in these results according to stage or IPS. Conclusion: There is no evidence of a difference in PFS and OS between SV and ABVD in this trial, which made extensive use of consolidation radiotherapy and included a relatively favourable cohort. More pulmonary toxicity was reported for ABVD, while other toxicities were slightly higher with S V.