Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.
Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.
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DOI：
10.1200/jco.2014.60.0734
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发表时间：
2015-07-10
期刊：
影响因子：
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通讯作者：
EURAMOS-1 investigators
中科院分区：
文献类型：
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作者：
Bielack SS;Smeland S;Whelan JS;Marina N;Jovic G;Hook JM;Krailo MD;Gebhardt M;Pápai Z;Meyer J;Nadel H;Randall RL;Deffenbaugh C;Nagarajan R;Brennan B;Letson GD;Teot LA;Goorin A;Baumhoer D;Kager L;Werner M;Lau CC;Sundby Hall K;Gelderblom H;Meyers P;Gorlick R;Windhager R;Helmke K;Eriksson M;Hoogerbrugge PM;Schomberg P;Tunn PU;Kühne T;Jürgens H;van den Berg H;Böhling T;Picton S;Renard M;Reichardt P;Gerss J;Butterfass-Bahloul T;Morris C;Hogendoorn PC;Seddon B;Calaminus G;Michelagnoli M;Dhooge C;Sydes MR;Bernstein M;EURAMOS-1 investigators
EURAMOS-1是一项国际随机对照试验，研究了聚乙二醇干扰素α-2b（IFN-α-2b）在骨肉瘤患者中的维持治疗，这些患者对诱导化疗表现出良好的组织学反应（良好反应）。诊断时，登记了年龄≤ 40岁的可切除高级别骨肉瘤患者。术后良好反应随机分配的合格性包括术前MAP（甲氨蝶呤、多柔比星和顺铂）≥ 2个周期、原发性肿瘤肉眼完全手术、存活肿瘤< 10%和无疾病进展。这些患者被随机分配到另外4个周期的MAP加或不加IFN-α-2b（0.5 - 1.0 μg/kg/周皮下注射，化疗后直至登记后2年）。结果指标为无事件生存期（EFS;主要）和总生存期和毒性（次要）。在2,260例登记患者中，1,041例报告了良好的反应; 716例同意随机分配（MAP，n = 359; MAP + IFN-α-2b，n = 357），基线特征按组平衡。357例中共有271例开始IFN-α-2b治疗; 105例提前停止治疗，38例在数据冻结时继续接受治疗。拒绝和毒性分别是从未开始使用IFN-α-2b和过早停止使用IFN-α-2b的主要原因。如果开始，中位IFN-α-2b持续时间为67周。在268例开始IFN-α-2b治疗并提供毒性信息的患者中，共有133例报告了IFN-α-2b治疗期间≥ 3级的毒性。中位随访时间为44个月，所有716例随机分配患者的3年EFS为76%（95% CI，72%-79%）;报告了174起EFS事件（MAP，n = 93; MAP + IFN-α-2b，n = 81）。校正后的考克斯模型的风险比为0.83（95% CI，0.61 - 1.12; P = 0.214）。在预先计划的分析时间，MAP + IFN-α-2b与单独MAP无统计学差异。相当大比例的患者从未开始使用IFN-α-2b或过早停止。继续对事件和生存进行长期随访。
EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.