Chemotherapy options in patients with advanced soft tissue sarcomas (STS) remain presently inadequate. In this phase II study the activity and toxicity of a combined alternating VAC/IE regimen in advanced and/or metastatic STS was evaluated. VAC (vincristine, total dose of 2 mg, adriamycin 70 mg/m2 and cyclophosphamide 600 mg/m2) was given as intravenous bolus infusion on day 1, followed after 21 days by IE (ifosfamide, 1.8 g/m2 infused over 1 h, daily for 5 consecutive days, with mesna uroprotection, plus etoposide at 500 mg/m2 infused over 2 h on the first day). Courses were repeated every 3 weeks. Twenty patients were treated, 12 of whom had previously been given chemotherapy for advanced and/or metastatic disease. Treatment was feasible in ambulatory setting, with good patient compliance. Myelosuppression, overall acceptable, was the major dose-limiting toxicity, while non-hematological side effects were minimal. An overall response rate of 45% was observed (95% CI, 26%-66%), with 2 complete and 7 partial remissions, achieving 75% in the subset of untreated patients. Median survival time was 10 months in the whole group (range, 4-26+ months) and 14 months in responder patients (range, 9-26+ months).