Originally published as JCO Early Release 10.1200/JCO.2004.00.5785 on October 24 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferrari, S. Articles by Sæter, G. Search for Related Content PubMed PubMed Citation Articles by Ferrari, S. Articles by Sæter, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Bone Cancer Hazardous Substances DB CIS-DIAMINEDICHLOROPLATINUM DOXORUBICIN IFOSFAMIDE METHOTREXATE PLATINUM COMPOUNDS Social Bookmarking                            What's this?

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

From the Chemotherapy, Surgery, Pathology, and Basic Research Divisions of the Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna; Oncologic/Orthopaedic Surgery, Centro Traumatologico Ortopedico, Firenze; Department of Pediatric Oncology, Meyer Hospital, Firenze; Department of Medical Oncology, S Maria delle Croci Hospital, Ravenna; Department of Oncology, Gradenigo Hospital; Department of Pediatric Oncology, Ospedale Regina Margherita, Torino, Italy; Department of Medical Oncology, The Norwegian Radium Hospital, Oslo, Norway; Department of Cancer Epidemiology, and Paediatric Oncology, Lund University Hospital, Lund; Department of Orthopaedics, Karolinska Hospital, Stockholm, Sweden; and Department of Pathology, Haartman Institute, Helsinki, Finland.

Address reprint requests to Stefano Ferrari, MD, Chemotherapy, Istituti Ortopedici Rizzoli, Via C. Pupilli 1, 40136 Bologna, Italy; e-mail: stefano.ferrari{at}ior.it

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/m²), methotrexate (12 g/m²), cisplatin (120 mg/m²), and doxorubicin (75 mg/m²). Postoperatively, patients received two cycles of doxorubicin (90 mg/m²), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m²). 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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. Picci, M. Mercuri, S. Ferrari, M. Alberghini, A. Briccoli, C. Ferrari, E. Pignotti, and G. Bacci Survival in high-grade osteosarcoma: improvement over 21 years at a single institution Ann. Onc., November 4, 2009; (2009) mdp502v1. [Abstract] [Full Text] [PDF]

				P. J. Messerschmitt, R. M. Garcia, F. W. Abdul-Karim, E. M. Greenfield, and P. J. Getty Osteosarcoma J. Am. Acad. Ortho. Surg., August 1, 2009; 17(8): 515 - 527. [Abstract] [Full Text] [PDF]

				S. Bielack, D. Carrle, P. G. Casali, and On behalf of the ESMO Guidelines Working Group Osteosarcoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv137 - iv139. [Full Text] [PDF]

				H. Imran, F. Enders, M. Krailo, F. Sim, S. Okuno, D. Hawkins, J. Neglia, R. L. Randall, R. Womer, L. Mascarenhas, et al. Effect of Time to Resumption of Chemotherapy After Definitive Surgery on Prognosis for Non-Metastatic Osteosarcoma J. Bone Joint Surg. Am., March 1, 2009; 91(3): 604 - 612. [Abstract] [Full Text] [PDF]

				A. Longhi, C. Errani, D. Gonzales-Arabio, C. Ferrari, and M. Mercuri Osteosarcoma in Patients Older Than 65 Years J. Clin. Oncol., November 20, 2008; 26(33): 5368 - 5373. [Abstract] [Full Text] [PDF]

				I. Scionti, F. Michelacci, M. Pasello, C. M. Hattinger, M. Alberghini, M. C. Manara, G. Bacci, S. Ferrari, K. Scotlandi, P. Picci, et al. Clinical impact of the methotrexate resistance-associated genes C-MYC and dihydrofolate reductase (DHFR) in high-grade osteosarcoma Ann. Onc., August 1, 2008; 19(8): 1500 - 1508. [Abstract] [Full Text] [PDF]

				L. H. Aksnes, H. C. F. Bauer, N. L. Jebsen, G. Folleras, C. Allert, G. S. Haugen, and K. S. Hall Limb-sparing surgery preserves more function than amputation: A SCANDINAVIAN SARCOMA GROUP STUDY OF 118 PATIENTS J Bone Joint Surg Br, June 1, 2008; 90-B(6): 786 - 794. [Abstract] [Full Text] [PDF]

				V. O. Lewis What's New in Musculoskeletal Oncology J. Bone Joint Surg. Am., June 1, 2007; 89(6): 1399 - 1407. [Full Text] [PDF]

				R. Yang, E. A. Kolb, J. Qin, A. Chou, R. Sowers, B. Hoang, J. H. Healey, A. G. Huvos, P. A. Meyers, and R. Gorlick The Folate Receptor {alpha} Is Frequently Overexpressed in Osteosarcoma Samples and Plays a Role in the Uptake of the Physiologic Substrate 5-Methyltetrahydrofolate Clin. Cancer Res., May 1, 2007; 13(9): 2557 - 2567. [Abstract] [Full Text] [PDF]

				M. J. Hicks, J. R. Roth, C. A. Kozinetz, and L. L. Wang Clinicopathologic Features of Osteosarcoma in Patients With Rothmund-Thomson Syndrome J. Clin. Oncol., February 1, 2007; 25(4): 370 - 375. [Abstract] [Full Text] [PDF]

				I. J. Lewis, M. A. Nooij, J. Whelan, M. R. Sydes, R. Grimer, P. C. W. Hogendoorn, M. A. Memon, S. Weeden, B. M. Uscinska, M. van Glabbeke, et al. Improvement in Histologic Response But Not Survival in Osteosarcoma Patients Treated With Intensified Chemotherapy: A Randomized Phase III Trial of the European Osteosarcoma Intergroup J Natl Cancer Inst, January 17, 2007; 99(2): 112 - 128. [Abstract] [Full Text] [PDF]