Comparison of long-term outcome between doublet versus triplet neoadjuvant chemotherapy in nonmetastatic osteosarcoma of extremity

Abstract

10542 Background: Multimodal approach had improved outcomes of non-metastatic osteosarcoma. This study was to compare outcomes between doublet (AP; doxorubicin and cisplatin) and triplet (IAP; AP and ifosfamide) neoadjuvant chemotherapy for non-meteastatic osteosarcoma of extremity in a single institute. Methods: A total of 124 osteosarcoma patients were enrolled. In AP group, doublet regimen was given to 77 patients from 1991 to 1999, who received intra-arterial cisplatin(120mg/m2) at day 1 and intravenous doxorubicin (25mg/m2) for 3 days. In IAP group, triplet regimen was given to 49 patients from 2000 to 2007, who received ifosfamide additionally at a dose of 2.5g/m2/day for 3 days. After completion of 3 cycles of chemotherapy, patients underwent limb-salvage surgery. We assessed tumor response according to pathologic tumor necrosis, and treated further adjuvant chemotherapy. In AP group, responder received 3 more cycles of AP, while non-responders received 6 cycles of ifosfamide-contaning regimens. In IAP group, all patients had 3 more cycles of IAP chemotherapy. Results: The median follow-up duration was 5.2 years (0.4–16.7). The most frequent site and histology were distal femur and osteoblastic type. Overall pathologic response was more than 90% tumor necrosis in 74.8% of patients. Total necrosis of tumor was also found in 46 patients (37.4%). There was no difference between two groups in pathologic response (76.3% vs. 72.3%; p=0.62) or other clinico-pathologic parameters. Tumor recurrence was occurred in 31.5% of patients with the most common site of lung (84.6%). There was no difference between two groups in recurrence (p=0.17) or lung metastasis (p=0.53). There were no statistical differences in disease free survival (p=0.75) and overall survival (p=0.07) between two groups. In toxicity profiles, there were more hematologic toxicity in IAP group (febrile neutropenia,p<0.001; thrombocytopenia,p<0.05), while there were no statistical differences in treatment related death. Conclusions: The addition of ifosfamide to doxorubicin and cisplatin in neoadjuvant chemotherapy did not show improved outcomes in this study. Further trials are required to elucidate optimal neoadjuvant chemotherapy and effective salvage regimens. No significant financial relationships to disclose.