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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;
- Meyer, James;
- Nadel, Helen;
- Randall, R Lor;
- Deffenbaugh, Claudia;
- Nagarajan, Rajaram;
- Brennan, Bernadette;
- Letson, G Douglas;
- Teot, Lisa A;
- Goorin, Allen;
- Baumhoer, Daniel;
- Kager, Leo;
- Werner, Mathias;
- Lau, Ching C;
- Hall, Kirsten Sundby;
- Gelderblom, Hans;
- Meyers, Paul;
- Gorlick, Richard;
- Windhager, Reinhard;
- Helmke, Knut;
- Eriksson, Mikael;
- Hoogerbrugge, Peter M;
- Schomberg, Paula;
- Tunn, Per-Ulf;
- Kühne, Thomas;
- Jürgens, Heribert;
- van den Berg, Henk;
- Böhling, Tom;
- Picton, Susan;
- Renard, Marleen;
- Reichardt, Peter;
- Gerss, Joachim;
- Butterfass-Bahloul, Trude;
- Morris, Carol;
- Hogendoorn, Pancras CW;
- Seddon, Beatrice;
- Calaminus, Gabriele;
- Michelagnoli, Maria;
- Dhooge, Catharina;
- Sydes, Matthew R;
- Bernstein, Mark
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.