1. 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
- Author
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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, Sundby Hall, Kirsten, 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 C W, Seddon, Beatrice, Calaminus, Gabriele, Michelagnoli, Maria, Dhooge, Catharina, Sydes, Matthew R, Bernstein, Mark, 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, Sundby Hall, Kirsten, 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 C W, Seddon, Beatrice, Calaminus, Gabriele, Michelagnoli, Maria, Dhooge, Catharina, Sydes, Matthew R, and 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
- Published
- 2015