Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas.IFO dose was 2 g/m2 on day 1-5 (with mesna uroprotection),ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1-5.G-CSF (2 μg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade Ⅳ neutropenia, 46/120 (38%) cycles had grade Ⅲ neutropenia. No patients had treatmentrelated deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity.Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.