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 Journal Article
| Authors: | Bielack, S. S.; Werner, M.; Tunn, P. U.; Helmke, K.; Jürgens, H.; Calaminus, G.; Gerss, J.; Butterfass-Bahloul, T.; Reichardt, P.; Smeland, S.; Hall, K. S.; Whelan, J. S.; Jovic, G.; Hook, J. M.; Sydes, M. R.; Seddon, B.; Michelagnoli, M.; Brennan, B.; Picton, S.; Marina, N.; Deffenbaugh, C.; Krailo, M. D.; Gebhardt, M.; Goorin, A.; Teot, L. A.; Pápai, Z.; Meyer, J.; Nadel, H.; Bernstein, M.; Randall, R. L.; Nagarajan, R.; Letson, G. D.; Baumhoer, D.; Kühne, T.; Kager, L.; Windhager, R.; Lau, C. C.; Gelderblom, H.; Hogendoorn, P. C. W.; Hoogerbrugge, P. M.; Van Den Berg, H.; Meyers, P.; Morris, C.; Gorlick, R.; Eriksson, M.; Schomberg, P.; Böhling, T.; Renard, M.; Dhooge, C. |
| Article 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 |
| 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. J Clin Oncol © 2015 American Society of Clinical Oncology. |
| Keywords: | osteosarcoma; adolescent; adult; child; controlled study; event free survival; treatment response; major clinical study; overall survival; fatigue; cisplatin; doxorubicin; diarrhea; drug efficacy; drug withdrawal; treatment duration; conference paper; methotrexate; outcome assessment; follow up; cancer grading; peginterferon alpha2b; multiple cycle treatment; mucosa inflammation; randomized controlled trial; vomiting; myalgia; maintenance therapy; chill; drug dose escalation; drug fever; depression; rigor; limb pain; flu like syndrome; headache; hazard ratio; phase 3 clinical trial; heart arrhythmia; treatment refusal; induction chemotherapy; thyroid disease; left ventricular systolic dysfunction; human; male; female; priority journal; joint effusion |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 33 |
| Issue: | 20 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2015-07-10 |
| Start Page: | 2279 |
| End Page: | 2287 |
| Language: | English |
| DOI: | 10.1200/jco.2014.60.0734 |
| PROVIDER: | scopus |
| PMCID: | PMC4486345 |
| PUBMED: | 26033801 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
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