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

EURAMOS-1 investigators

Research output: Contribution to journalArticle

Abstract

Purpose: 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. 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-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). Results: 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. Conclusion: 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. J Clin Oncol

Original languageEnglish (US)
Pages (from-to)2279-2287
Number of pages9
JournalJournal of Clinical Oncology
Volume33
Issue number20
DOIs
StatePublished - Jul 10 2015
Externally publishedYes

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interferon alfa-2b
Osteosarcoma
Methotrexate
Doxorubicin
Cisplatin
Randomized Controlled Trials
Maintenance
peginterferon alfa-2b
Induction Chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{d3ec8563da734183b000bb070908ac68,
title = "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",
abstract = "Purpose: 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. 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-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). Results: 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. Conclusion: 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. J Clin Oncol",
author = "{EURAMOS-1 investigators} and Bielack, {Stefan S.} and Mathias Werner and Tunn, {Per Ulf} and Knut Helmke and Heribert J{\"u}rgens and Gabriele Calaminus and Joachim Gerss and Trude Butterfass-Bahloul and Peter Reichardt and Sigbj{\o}rn Smeland and Hall, {Kirsten Sundby} and Whelan, {Jeremy S.} and Gordana Jovic and Hook, {Jane M.} and Sydes, {Matthew R.} and Beatrice Seddon and Maria Michelagnoli and Bernadette Brennan and Susan Picton and Neyssa Marina and Claudia Deffenbaugh and Krailo, {Mark D.} and Mark Gebhardt and Allen Goorin and Teot, {Lisa A.} and Zsuzsanna P{\'a}pai and James Meyer and Helen Nadel and Mark Bernstein and Randall, {R. Lor} and Rajaram Nagarajan and Letson, {G. Douglas} and Daniel Baumhoer and Thomas K{\"u}hne and Leo Kager and Reinhard Windhager and Lau, {Ching C.} and Hans Gelderblom and Hogendoorn, {Pancras C W} and Hoogerbrugge, {Peter M.} and {Van Den Berg}, Henk and Paul Meyers and Morris, {Carol D} and Richard Gorlick and Mikael Eriksson and Paula Schomberg and Tom B{\"o}hling and Marleen Renard and Catharina Dhooge",
year = "2015",
month = "7",
day = "10",
doi = "10.1200/JCO.2014.60.0734",
language = "English (US)",
volume = "33",
pages = "2279--2287",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "20",

}

TY - JOUR

T1 - 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

T2 - First results of the EURAMOS-1 good response randomized controlled trial

AU - EURAMOS-1 investigators

AU - Bielack, Stefan S.

AU - Werner, Mathias

AU - Tunn, Per Ulf

AU - Helmke, Knut

AU - Jürgens, Heribert

AU - Calaminus, Gabriele

AU - Gerss, Joachim

AU - Butterfass-Bahloul, Trude

AU - Reichardt, Peter

AU - Smeland, Sigbjørn

AU - Hall, Kirsten Sundby

AU - Whelan, Jeremy S.

AU - Jovic, Gordana

AU - Hook, Jane M.

AU - Sydes, Matthew R.

AU - Seddon, Beatrice

AU - Michelagnoli, Maria

AU - Brennan, Bernadette

AU - Picton, Susan

AU - Marina, Neyssa

AU - Deffenbaugh, Claudia

AU - Krailo, Mark D.

AU - Gebhardt, Mark

AU - Goorin, Allen

AU - Teot, Lisa A.

AU - Pápai, Zsuzsanna

AU - Meyer, James

AU - Nadel, Helen

AU - Bernstein, Mark

AU - Randall, R. Lor

AU - Nagarajan, Rajaram

AU - Letson, G. Douglas

AU - Baumhoer, Daniel

AU - Kühne, Thomas

AU - Kager, Leo

AU - Windhager, Reinhard

AU - Lau, Ching C.

AU - Gelderblom, Hans

AU - Hogendoorn, Pancras C W

AU - Hoogerbrugge, Peter M.

AU - Van Den Berg, Henk

AU - Meyers, Paul

AU - Morris, Carol D

AU - Gorlick, Richard

AU - Eriksson, Mikael

AU - Schomberg, Paula

AU - Böhling, Tom

AU - Renard, Marleen

AU - Dhooge, Catharina

PY - 2015/7/10

Y1 - 2015/7/10

N2 - Purpose: 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. 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-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). Results: 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. Conclusion: 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. J Clin Oncol

AB - Purpose: 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. 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-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). Results: 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. Conclusion: 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. J Clin Oncol

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U2 - 10.1200/JCO.2014.60.0734

DO - 10.1200/JCO.2014.60.0734

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VL - 33

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EP - 2287

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 20

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