{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:22:25Z","timestamp":1789986145090,"version":"4.0.1"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:p> PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. <\/jats:p><jats:p> PATIENTS AND METHODS: Eligible patients received infusions of 100 mg\/m<jats:sup>2<\/jats:sup> per day of etoposide and 3.5 g\/m<jats:sup>2<\/jats:sup> per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. <\/jats:p><jats:p> RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% \u00b1 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% \u00b1 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% \u00b1 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi\u2019s syndrome was observed in five patients. <\/jats:p><jats:p> CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity. <\/jats:p>","DOI":"10.1200\/jco.2002.20.2.426","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T07:59:20Z","timestamp":1487923160000},"page":"426-433","source":"Crossref","is-referenced-by-count":268,"title":["Phase II\/III Trial of Etoposide and High-Dose Ifosfamide in Newly Diagnosed Metastatic Osteosarcoma: A Pediatric Oncology Group Trial"],"prefix":"10.1200","volume":"20","author":[{"given":"Allen M.","family":"Goorin","sequence":"first","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Harris","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bernstein","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Ferguson","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Devidas","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene P.","family":"Siegal","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; Tomorrow\u2019s Children Institute, Hackensack, and University of Medicine and Dentistry of New Jersey, Hackensack, NJ; Hematology-Oncology, Ste Justine Hospital; University of Montreal, Montreal, Quebec, Canada; Brown Medical School, Division of Pediatric-Hematology-Oncology, Rhode Island Hospital, Providence, RI; Department of Statistics, University of Florida, and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Gebhardt","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, The Children\u2019s Hospital, and Massachusetts General Hospital, Harvard Medical School, Boston, MA; 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