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

被引：320

作者：

Bielack, Stefan S. ^{[1
]}

Smeland, Sigbjorn ^{[7
]}

Whelan, Jeremy S. ^{[9
]}

Marina, Neyssa ^{[15
]}

Jovic, Gordana ^{[10
]}

Hook, Jane M. ^{[10
]}

Krailo, Mark D. ^{[17
]}

Gebhardt, Mark ^{[18
,19
]}

Papai, Zsuzsanna ^{[20
]}

Meyer, James ^{[21
,22
]}

Nadel, Helen ^{[23
,24
]}

Randall, R. Lor ^{[26
]}

Deffenbaugh, Claudia ^{[16
]}

Nagarajan, Rajaram ^{[27
]}

Brennan, Bernadette ^{[12
,13
]}

Letson, G. Douglas ^{[28
]}

Teot, Lisa A. ^{[19
]}

Goorin, Allen ^{[18
]}

Baumhoer, Daniel ^{[29
]}

Kager, Leo ^{[31
]}

Werner, Mathias ^{[2
]}

Lau, Ching C. ^{[33
]}

Hall, Kirsten Sundby ^{[7
,8
]}

Gelderblom, Hans ^{[34
]}

Meyers, Paul ^{[37
]}

Gorlick, Richard ^{[38
]}

Windhager, Reinhard ^{[32
]}

Helmke, Knut ^{[4
]}

Eriksson, Mikael ^{[39
]}

Hoogerbrugge, Peter M. ^{[35
]}

Schomberg, Paula ^{[40
]}

Tunn, Per-Ulf ^{[3
]}

Kuehne, Thomas ^{[30
]}

Juergens, Heribert ^{[5
]}

van den Berg, Henk ^{[36
]}

Bohling, Tom ^{[41
,42
,43
]}

Picton, Susan ^{[14
]}

Renard, Marleen ^{[44
]}

Reichardt, Peter ^{[6
]}

Gerss, Joachim ^{[5
]}

Butterfass-Bahloul, Trude ^{[5
]}

Morris, Carol ^{[37
]}

Hogendoorn, Pancras C. W. ^{[34
]}

Seddon, Beatrice ^{[11
]}

Calaminus, Gabriele ^{[5
]}

Michelagnoli, Maria ^{[11
]}

Dhooge, Catharina ^{[45
]}

Sydes, Matthew R. ^{[10
]}

Bernstein, Mark ^{[25
]}

机构：

[1] Olga Hosp, Klinikum Stuttgart, Stuttgart, Germany

[2] Helios Klinikum Emil Von Behring, Berlin, Germany

[3] Helios Klinikum Berlin Buch, Berlin, Germany

[4] Altonaer Kinderkrankenhaus, Hamburg, Germany

[5] Univ Klinikum Munster, Munster, Germany

[6] Klin Interdisziplinare Onkol, Bad Saarow Pieskow, Germany

[7] Oslo Univ Hosp, Oslo, Norway

[8] Norwegian Radium Hosp, Oslo, Norway

[9] Univ Coll London Hosp, London, England

[10] UCL, London WC1E 6BT, England

[11] Univ Coll Hosp, London, England

[12] Christie Hosp, Manchester, England

[13] Royal Manchester Childrens Hosp, Manchester, England

[14] Univ Leeds, Leeds, W Yorkshire, England

[15] Stanford Univ, Med Ctr, Stanford, CA 94305 USA

[16] Lucille Salter Packard Childrens Hosp, Palo Alto, CA USA

[17] Childrens Oncol Grp, Arcadia, CA USA

[18] Dana Farber Canc Inst, Boston, MA USA

[19] Childrens Hosp, Boston, MA 02115 USA

[20] Natl Med Ctr, Budapest, Hungary

[21] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[22] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[23] British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada

[24] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[25] Dalhousie Univ, Halifax, NS, Canada

[26] Univ Utah, Salt Lake City, UT USA

[27] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[28] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[29] Univ Spital Basel, Basel, Switzerland

[30] Univ Childrens Hosp Basel, Basel, Switzerland

[31] St Annas Children Hosp, Vienna, Austria

[32] Med Univ Vienna, Vienna, Austria

[33] Baylor Coll Med, Houston, TX 77030 USA

[34] Leiden Univ, Med Ctr, Leiden, Netherlands

[35] Radbound Univ Nijmegen, Med Ctr, Nijmegen, Netherlands

[36] Emma Childrens Hosp, Acad Med Ctr, Amsterdam, Netherlands

[37] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[38] Montefiore Med Ctr, Bronx, NY 10467 USA

[39] Skane Univ Hosp, Lund, Sweden

[40] Mayo Clin, Rochester, MN USA

[41] Univ Helsinki, Helsinki, Finland

[42] Hosp Dist Helsinki, Helsinki, Finland

[43] Uusimaa Lab, Helsinki, Finland

[44] Univ Hosp Leuven, Leuven, Belgium

[45] Univ Hosp, Ghent, Belgium

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 20期

基金：

英国医学研究理事会; 芬兰科学院;

关键词：

MURAMYL TRIPEPTIDE; ADJUVANT TREATMENT; CLINICAL-TRIALS; SURVIVAL; THERAPY; CANCER; ALPHA; IFOSFAMIDE; DURATION;

D O I：

10.1200/JCO.2014.60.0734

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-alpha-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods 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-alpha-2b (0.5 to 1.0 mu g/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-alpha-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-alpha-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-alpha-2b and for stopping prematurely, respectively. Median IFN-alpha-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-alpha-2b and provided toxicity information reported grade >= 3 toxicity during IFN-alpha-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-alpha-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-alpha-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-alpha-2b or stopped prematurely. Long-term follow-up for events and survival continues. (C) 2015 American Society of Clinical Oncology.

引用

页码：2279 / U92

页数：20

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