Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: A joint study by the Italian and Scandinavian Sarcoma Groups

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@article{08eb1131377040939f770a8341c4fddc,
title = "Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: A joint study by the Italian and Scandinavian Sarcoma Groups",
abstract = "Purpose To explore the effect of high-dose ifosfamide in first-line treatment for patients <= 40 years of age with nonmetastatic osteosarcoma of the extremity. Patients and Methods From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m(2)), methotrexate (12 g/m(2)), cisplatin (120 mg/m(2)), and doxorubicin (75 mg/m(2)). Postoperatively, patients received two cycles of doxorubicin (go mg/m(2)), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m(2)). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination. Results No disease progression was recorded during primary chemotherapy, 164 patients (92{\%}) underwent limb-salvage surgery, four patients (2{\%}) underwent rotation plasty, and 11 patients (6{\%}) had limbs amputated. Three (1.6{\%}) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52{\%} and 31{\%} of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10{\%}). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64{\%} (95{\%} CI 57{\%} to 71{\%}) and overall survival was 77{\%} (95{\%} CI 67{\%} to 81{\%}), whereas seven patients (4{\%}) experienced local recurrence. Conclusion The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90{\%} of patients with osteosarcoma of the extremity can undergo conservative surgery.",
author = "S Ferrari and S Smeland and M Mercuri and F Bertoni and A Longhi and P Ruggieri and Thor Alveg{\aa}rd and P Picci and R Capanna and G Bernini and C Muller and A Tienghi and Thomas Wiebe and A Comandone and T Bohling and {Del Prever}, AB and O Brosjo and G Bacci and G Saeter",
year = "2005",
doi = "10.1200/JCO.2004.00.5785",
language = "English",
volume = "23",
pages = "8845--8852",
journal = "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
issn = "1527-7755",
publisher = "American Society of Clinical Oncology",
number = "34",

}