Neo-adjuvant chemotherapy for limb preservation in non-metastatic osteosarcoma of the extremity: AIIMS experience

Abstract

9056 Background: Osteosarcoma is the most common primary malignant neoplasm of bone in children and adolescents. The purpose of this study was to determine the optimal therapy and feasibility of limb salvage in patients with localized non metastatic osteosarcoma. Methods: In a prospective single arm study between January 1999 to July 2004 newly diagnosed patients presenting with localized osteosarcoma of the extremity received 3 cycles of neoadjuvant chemotherapy with CAMP i.e. cyclophosphamide (700mg/m2 IV day1), adriamycin (50mg/m2 IV day1), cisplatin (100mg/m2 over 3 days) and methotrexate (175mg/m2 IV day1) with leucovorin rescue followed by definitive surgery. Adjuvant therapy consisted of 3 cycles with CAMP in good responders (>/=90%necrosis) whereas poor responders received ifosfamide, etoposide and cisplatin. Endpoints studied were response to chemotherapy, rate of limb salvage and treatment toxicity. Survival was obtained using Kaplan-Mier estimates. Results: 65 patients were available for analysis. The median age was 18 years (range 9–36 years). Cortical destruction and soft tissue extension of tumor was present in all cases. 35 patients (54%) underwent limb salvage surgery whereas 30 (46%) required amputation. Post surgical margins were positive in 2 cases and the degree of necrosis was >/=90% in 27(42%) cases. The incidence of grade 3 and 4 hematological toxicity was 38% and 9% respectively. Grade 2 GI toxicity was observed in 75% cases. There was no treatment related mortality. 24 patients relapsed, 3 at both local and distant sites and 21 with distant metastasis in the lungs. The 5-year overall and disease free survival were 72% and 63% respectively. The most significant prognostic factors that emerged were the response to neoadjuvant chemotherapy (p=0.003) and the post surgical margin status (p<0.01). Conclusions: Osteosarcoma continues to be a challenge in developing countries with many patients presenting in advanced stages and being unable to afford expensive treatment. Never the less our experience has shown that they can be effectively treated with neoadjuvant and adjuvant chemotherapy with limb sparing surgery. No significant financial relationships to disclose.