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
-
Bielack, S.S., Smeland, S., Whelan, J.S., Marina, N., Jovic, G., Hook, J.M., Krailo, M.D., Gebhardt, M., Papai, Z., Meyer, J., Nadel, H., Randall, R.L., Deffenbaugh, C., Nagarajan, R., Brennan, B., Letson, G.D., Teot, L.A., Goorin, A., Baumhoer, D., Kager, L., Werner, M., Lau, C.C., Hall, K.S., Gelderblom, H., Meyers, P., Gorlick, R., Windhager, R., Helmke, K., Eriksson, M., Hoogerbrugge, P.M., Schomberg, P., Tunn, P.U., Kuhne, T., Jurgens, H., Berg, H. van den, Bohling, T., Picton, S., Renard, M., Reichardt, P., Gerss, J., Butterfass-Bahloul, T., Morris, C., Hogendoorn, P.C.W., Seddon, B., Calaminus, G., Michelagnoli, M., Dhooge, C., Sydes, M.R., Bernstein, M., and EURAMOS-1 Investigators
- Subjects
Adult ,Male ,Asia ,Time Factors ,Adolescent ,Clinical Sciences ,Oncology and Carcinogenesis ,EURAMOS-1 investigators ,Bone Neoplasms ,Kaplan-Meier Estimate ,Interferon alpha-2 ,Disease-Free Survival ,Polyethylene Glycols ,Young Adult ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Chemotherapy ,Humans ,Oncology & Carcinogenesis ,Preschool ,Child ,Adjuvant ,Proportional Hazards Models ,Osteosarcoma ,Errata ,Australia ,Interferon-alpha ,Neoadjuvant Therapy ,Recombinant Proteins ,Osteotomy ,Europe ,Methotrexate ,Treatment Outcome ,Chemotherapy, Adjuvant ,Doxorubicin ,Child, Preschool ,North America ,Disease Progression ,Female ,Cisplatin ,Neoplasm Grading - Abstract
PurposeEURAMOS-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 methodsAt 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).ResultsGood 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.ConclusionAt 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.
- Published
- 2015