Results of the EICESS-92 study:: Two randomized trials of Ewing's sarcoma treatment -: Cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients
Results of the EICESS-92 study:: Two randomized trials of Ewing's sarcoma treatment -: Cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients
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DOI：
10.1200/jco.2008.16.5720
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发表时间：
2008-09-20
影响因子：
45.3
通讯作者：
Juergens, Herbert
中科院分区：
文献类型：
--
作者：
Paulussen, Michael;Craft, Alan W.;Juergens, Herbert
欧洲尤文氏肉瘤研究调查了环磷酰胺在标准风险（SR）患者中是否具有与异环磷酰胺相似的疗效，以及添加依托泊苷是否改善高危（HR）患者的生存率。（局部肿瘤，体积< 100 mL）随机分配接受长春新碱，更生霉素，异环磷酰胺，和多柔比星（VAIA）诱导治疗，随后进行10个疗程的VAIA或长春新碱、更生霉素、环磷酰胺和多柔比星（VACA;环磷酰胺替代异环磷酰胺）。HR患者（体积>= 100 mL或转移）被随机分配接受14个疗程的VAIA或VAIA加依托泊苷（EVAIA）。结果的措施是无事件生存期（EFS，定义为第一次复发，进展，第二恶性肿瘤，或死亡的时间）和总生存期（OS）。ResultsA共647例患者被随机分配：79 SR患者被分配到VAIA，76 SR患者被分配到VACA，240 HR被分配到VAIA，和252 HR患者被分配到EVAIA。中位随访时间为8.5年。在SR组中，EFS和OS的风险比（VACA vs VAIA）分别为0.91（95% CI，0.55 - 1.53）和1.08（95% CI，0.58 - 2.03）。VACA组的血液学毒性发生率较高。HR组的EFS和OS风险比（EVAIA vs VAIA）分别显示事件风险降低17%（95% CI，-35%至5%; P = 0.12）和死亡风险降低15%（95% CI，-34%至10%）。没有转移的患者（风险比= 0.79; P = 0.16）比那些有转移（风险比= 0.96; P = 0.84）的效果似乎更大。结论环磷酰胺似乎有一个类似的影响EFS和OS异环磷酰胺在SR患者，但与毒性增加。在HR患者中，添加依托泊苷似乎是有益的。
PurposeThe European Intergroup Cooperative Ewing's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk (SR) patients and whether the addition of etoposide improves survival in high-risk (HR) patients.Patients and MethodsSR patients (localized tumors, volume < 100 mL) were randomly assigned to receive four courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume >= 100 mL or metastases) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival (EFS; defined as the time to first recurrence, progression, second malignancy, or death) and overall survival (OS).ResultsA total of 647 patients were randomly assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA. The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to 2.03), respectively. There was a higher incidence of hematologic toxicities in the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA) indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12) and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed greater among patients without metastases (hazard ratio = 0.79; P = .16) than among those with metastases (hazard ratio = 0.96; P = .84).ConclusionCyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.