SY9-1 - Standard Therapy for Localized Soft Tissue Sarcomas

Abstract

Soft tissue sarcomas (STS) are very rare malignant tumors. Because of the rareness, it is difficult to develop new standard therapies for STS. According to the Soft Tissue Tumor Registry by the Japanese Orthopaedic Association, approximately 75% of the patients with STS exhibit the localized disease at first presentation. All localized STS should be treated by definitive surgery with appropriate margin as standard treatment. The low-grade, superficial or small STS can be cured by surgery alone. Insufficient surgical margin, including marginal or intra-lesional resection, may require adjuvant radiation therapy. On the other hand, high-grade, deep-seated and large, i.e., high-risk STS result in poor prognosis when they are treated by surgery alone. To establish the effective adjuvant chemotherapy for high-risk STS, a number of randomized clinical trials have been carried out. All the randomized studies, except one, failed to demonstrate the superiority of adjuvant chemotherapy in overall survival (OS) of the patients with localized STS in comparison with surgery alone. However, meta-analyses of the randomized trials have confirmed the significant improvement of OS by adjuvant chemotherapy for STS. Recently, a randomized study comparing neo-adjuvant full-dose epirubicin (EPI)+ifosfamide (IFM) and histology-tailored chemotherapy for high-risk STS conducted by the Italian Sarcoma Group has clearly showed the significantly better OS in EPI+IFM group. The result was comparable with that in a phase II trial, JCOG0304, using neo-adjuvant chemotherapy with doxorubicin (DOX)+IFM carried out by the Japan Clinical Oncology Group (JCOG). Thus, the current standard therapy for high-grade, deep-seated and large STS is the neo-adjuvant chemotherapy with full-dose DOX+IFM. We are currently conducting a randomized phase II/III study comparing the efficacy of neo-adjuvant DOX+IFM and gemcitabine+docetaxel for high-risk localized STS, JCOG1306.