Journal of Clinical Oncology · 2005 · 435 citations · 30 references
MedicineOncologySurgeryChemotherapyOncologic SurgerySurgical OncologyChemotherapy For Bone SarcomaCombination ChemotherapyHigh-dose ChemotherapyNeoadjuvant ChemotherapyNeoadjuvant PharmacotherapyNeoadjuvant TherapyAnthracycline-based ChemotherapyGranulocyte Colony-stimulating Factor AdministrationGranulocyte Colony-stimulating Factor MobilizationGranulocyte-macrophage Colony-stimulating Factor MobilizationHigh-dose Methotrexate TherapyIfosfamide-based TherapyOsteosarcoma ChemotherapyOsteosarcoma Treatment
The study aimed to evaluate high‑dose ifosfamide as first‑line therapy for patients ≤40 years with non‑metastatic extremity osteosarcoma. Patients received two preoperative blocks of high‑dose ifosfamide (15 g/m²), methotrexate (12 g/m²), cisplatin (120 mg/m²), and doxorubicin (75 mg/m²), followed by postoperative doxorubicin and additional cycles of the same agents, with mandatory G‑CSF support. The regimen was feasible, achieving 92 % limb‑salvage surgery, 1.6 % treatment‑related mortality, 10 % nephrotoxicity, 52 % grade 4 neutropenia, and a 5‑year event‑free survival of 64 % with overall survival of 77 %, but was associated with major renal and hematologic toxicities and did not improve survival over standard‑dose regimens.
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.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.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.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.
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Primary osteogenic sarcoma. The rationale for preoperative chemotherapy and delayed surgery
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Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial.
Frederick R. Eilber, A. E. Giuliano, J J Eckardt et al. · Journal of Clinical Oncology · 1987 · 531 citations
Adjuvant Methotrexate and Citrovorum-Factor Treatment of Osteogenic Sarcoma
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Medicine, Oncology, Pharmacology +11