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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.
J Clin Oncol 2005; 23(34):8845-52JC

Abstract

PURPOSE

To explore the effect of high-dose ifosfamide in first-line treatment for patients < or = 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+Show Affiliations

Chemotherapy Division of Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Via C. Pupilli 1, 40136 Bologna, Italy. stefano.ferrari@ior.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study

Language

eng

PubMed ID

16246977

Citation

Ferrari, Stefano, et al. "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." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 23, no. 34, 2005, pp. 8845-52.
Ferrari S, Smeland S, Mercuri M, et al. 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. J Clin Oncol. 2005;23(34):8845-52.
Ferrari, S., Smeland, S., Mercuri, M., Bertoni, F., Longhi, A., Ruggieri, P., ... Saeter, G. (2005). 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. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 23(34), pp. 8845-52.
Ferrari S, et al. 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. J Clin Oncol. 2005 Dec 1;23(34):8845-52. PubMed PMID: 16246977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ferrari,Stefano, AU - Smeland,Sigbjorn, AU - Mercuri,Mario, AU - Bertoni,Franco, AU - Longhi,Alessandra, AU - Ruggieri,Pietro, AU - Alvegard,Thor A, AU - Picci,Piero, AU - Capanna,Rodolfo, AU - Bernini,Gabriella, AU - Müller,Cristoph, AU - Tienghi,Amelia, AU - Wiebe,Thomas, AU - Comandone,Alessandro, AU - Böhling,Tom, AU - Del Prever,Adalberto Brach, AU - Brosjö,Otte, AU - Bacci,Gaetano, AU - Saeter,Gunnar, AU - ,, Y1 - 2005/10/24/ PY - 2005/10/26/pubmed PY - 2006/2/14/medline PY - 2005/10/26/entrez SP - 8845 EP - 52 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 23 IS - 34 N2 - PURPOSE: To explore the effect of high-dose ifosfamide in first-line treatment for patients < or = 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. SN - 0732-183X UR - https://www.unboundmedicine.com/medline/citation/16246977/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_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2004.00.5785?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -