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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

Bielack, Stefan S ; Smeland, Sigbjørn ; Whelan, Jeremy S ; Marina, Neyssa ; Jovic, Gordana ; Hook, Jane M ; Krailo, Mark D ; Gebhardt, Mark ; Pápai, Zsuzsanna and Meyer, James , et al. (2015) In Journal of Clinical Oncology 33(20). p.2279-2287
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... (More)
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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
33
issue
20
pages
2279 - 2287
publisher
American Society of Clinical Oncology
external identifiers
  • pmid:26033801
  • wos:000361653400008
  • scopus:84941276779
  • pmid:26033801
ISSN
1527-7755
DOI
10.1200/JCO.2014.60.0734
language
English
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yes
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d28df80f-9433-4f99-98e7-bd5b425390d9 (old id 7508515)
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http://www.ncbi.nlm.nih.gov/pubmed/26033801?dopt=Abstract
date added to LUP
2016-04-01 10:15:30
date last changed
2020-10-07 01:33:04
@article{d28df80f-9433-4f99-98e7-bd5b425390d9,
  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, &lt; 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.},
  author       = {Bielack, Stefan S and Smeland, Sigbjørn and Whelan, Jeremy S and Marina, Neyssa and Jovic, Gordana and Hook, Jane M and Krailo, Mark D and Gebhardt, Mark and Pápai, Zsuzsanna and Meyer, James and Nadel, Helen and Randall, R Lor and Deffenbaugh, Claudia and Nagarajan, Rajaram and Brennan, Bernadette and Letson, G Douglas and Teot, Lisa A and Goorin, Allen and Baumhoer, Daniel and Kager, Leo and Werner, Mathias and Lau, Ching C and Sundby Hall, Kirsten and Gelderblom, Hans and Meyers, Paul and Gorlick, Richard and Windhager, Reinhard and Helmke, Knut and Eriksson, Mikael and Hoogerbrugge, Peter M and Schomberg, Paula and Tunn, Per-Ulf and Kühne, Thomas and Jürgens, Heribert and van den Berg, Henk and Böhling, Tom and Picton, Susan and Renard, Marleen and Reichardt, Peter and Gerss, Joachim and Butterfass-Bahloul, Trude and Morris, Carol and Hogendoorn, Pancras C W and Seddon, Beatrice and Calaminus, Gabriele and Michelagnoli, Maria and Dhooge, Catharina and Sydes, Matthew R and Bernstein, Mark},
  issn         = {1527-7755},
  language     = {eng},
  number       = {20},
  pages        = {2279--2287},
  publisher    = {American Society of Clinical Oncology},
  series       = {Journal of Clinical Oncology},
  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},
  url          = {https://lup.lub.lu.se/search/ws/files/1692560/8560306},
  doi          = {10.1200/JCO.2014.60.0734},
  volume       = {33},
  year         = {2015},
}