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.
|
|---|---|
| Authors | Stefan S Bielack, Sigbjørn Smeland, Jeremy S Whelan, Neyssa Marina, Gordana Jovic, Jane M Hook, Mark D Krailo, Mark Gebhardt, Zsuzsanna Pápai, James Meyer, Helen Nadel, R Lor Randall, Claudia Deffenbaugh, Rajaram Nagarajan, Bernadette Brennan, G Douglas Letson, Lisa A Teot, Allen Goorin, Daniel Baumhoer, Leo Kager, Mathias Werner, Ching C Lau, Kirsten Sundby Hall, Hans Gelderblom, Paul Meyers, Richard Gorlick, Reinhard Windhager, Knut Helmke, Mikael Eriksson, Peter M Hoogerbrugge, Paula Schomberg, Per-Ulf Tunn, Thomas Kühne, Heribert Jürgens, Henk van den Berg, Tom Böhling, Susan Picton, Marleen Renard, Peter Reichardt, Joachim Gerss, Trude Butterfass-Bahloul, Carol Morris, Pancras C W Hogendoorn, Beatrice Seddon, Gabriele Calaminus, Maria Michelagnoli, Catharina Dhooge, Matthew R Sydes, Mark Bernstein, EURAMOS-1 investigators |
| Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 20 Pg. 2279-87 (Jul 10 2015) ISSN: 1527-7755 [Electronic] United States |
| PMID | 26033801 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Webcast) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!