Neoadjuvant and Adjuvant Cycles of Doxorubicin, Cisplatin, Ifosfamide and Etoposide in for Non-Metastatic Adolescent and Young Adult Osteosarcoma with Shift to Adjuvant Docetaxel and Gemcitabine in Poor Responders. Is Serum Insulin Like Growth Factor-1 Correlated to Treatment Outcome?

Purpose: To evaluate toxicity and efficacy of a non-methotrexate combination chemotherapy in osteosarcoma trying to avoid its toxicity. To make analysis of the Insulin Growth Factor-1 (IGF-1) as its signaling pathway is important in osteosarcoma.Methods: Nineteen patients with localized high grade conventional osteosarcoma of extremities between 15 and 25 years old, received neoadjuvant three (APIE) 28-day cycles,on day 1: Doxorubicin 75mg/m² Intravenous Infusion (IV) and cisplatin 120mg/m² IVI, on day 2-5: Etoposide 100mg/m² IVI and ifosfamide 2gm/m² continuous ivi with mesna. After surgery, Good Responders (GR) had 3 adjuvant cycles of same preoperative regimen while poor responders PR were shifted to 3 (GD) 28-day cycles of gemcitabine 675mg/m2 IVI on days 1 and 8 plus docetaxel 75mg/m2 IVI on day 8. All cycles were supported with filgrastim.Results: Treatment was tolerable. The most common significant toxicity was neutropenia G3-4 in (27%) of GR patients vs 38% of (PR). GR patients were 58% versus 42% PR. Limb salvage surgery was possible in 53% of cases, 5% underwent rotationplasty and 42% had amputation. The 5- year Event Free Survival (EFS) of all patients was: 59%±3, for (GR): 78%±5 and for (PR): 36%±13, p=0.03 (significant). The 5-year Overall Survival (OS) for all was 65%±4, for (GR): 78%±3, for (PR): 50%±15, p=0.11. No significant correlation was found between IGF-1 level and pathological response (p=0.76). The 5-year EFS for high and low serum IGF-1 cases: 52.5% and 66.7%, respectively, p=0.48, while the 5-year OS were: 48.7%, 69.4%, respectively, p=0.27.Conclusion: This regimen is an effective and tolerable for adult osteosarcoma. Analysis of IGF-1 and its pathway related proteins is needed in a larger numbers of cases.