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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

Ferrari, S ; Smeland, S ; Mercuri, M ; Bertoni, F ; Longhi, A ; Ruggieri, P ; Alvegård, Thor LU ; Picci, P ; Capanna, R and Bernini, G , et al. (2005) In Journal of Clinical Oncology 23(34). p.8845-8852
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
23
issue
34
pages
8845 - 8852
publisher
American Society of Clinical Oncology
external identifiers
  • wos:000233690200040
  • pmid:16246977
  • scopus:33644837672
ISSN
1527-7755
DOI
10.1200/JCO.2004.00.5785
language
English
LU publication?
yes
id
08eb1131-3770-4093-9f77-0a8341c4fddc (old id 211582)
date added to LUP
2016-04-01 12:18:47
date last changed
2022-03-28 23:13:18
@article{08eb1131-3770-4093-9f77-0a8341c4fddc,
  abstract     = {{Purpose To explore the effect of high-dose ifosfamide in first-line treatment for patients &lt;= 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       = {{Ferrari, S and Smeland, S and Mercuri, M and Bertoni, F and Longhi, A and Ruggieri, P and Alvegård, Thor and Picci, P and Capanna, R and Bernini, G and Muller, C and Tienghi, A and Wiebe, Thomas and Comandone, A and Bohling, T and Del Prever, AB and Brosjo, O and Bacci, G and Saeter, G}},
  issn         = {{1527-7755}},
  language     = {{eng}},
  number       = {{34}},
  pages        = {{8845--8852}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of Clinical Oncology}},
  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}},
  url          = {{http://dx.doi.org/10.1200/JCO.2004.00.5785}},
  doi          = {{10.1200/JCO.2004.00.5785}},
  volume       = {{23}},
  year         = {{2005}},
}