Dose-intensive first-line chemotherapy with epirubicin and continuous infusion ifosfamide in adult patients with advanced soft tissue sarcomas: a phase II study

This phase II study was designed to verify the activity and safety of an in tensive epirubicin/ifosfamide schedule in untreated soft tissue sarcoma (ST S) patients by using both the agents at the identified maximal tolerated do ses. 39 adult patients were treated with epirubicin at 55 mg/m(2), on days 1 and 2 (total dose per cycle 110 mg/m(2)) combined with ifosfamide at 2.5 g/m(2) days 1-4 (total dose per cycle 10 g/m(2)), with equidose mesna uropr otection and G-CSF support. Treatment was given on an ambulatory basis, at 3-week intervals. The overall objective response (OR) rate was 59% (95% con fidence interval, CI, 43-72%), with 5 complete responses (13%) and 18 parti al responses (46%); 12 partial responders were rendered disease-free follow ing surgery. The median survival time was 19 months, being 23 and 13 months , respectively, for responding and non-responding patients. The median time to response was 40 days (range 21-60). Treatment-related toxicity was over all acceptable. The OR of 59% was the highest ever reported in our consecut ive studies in advanced STS, confirming that improved therapeutic efficacy can be obtained with intensified regimens in such a disease; both the respo nse duration and survival were also longer. The observed activity proved to be interesting with regard to the high response rate in the lung (86%), as well as the proportion of patients rendered disease-free by early surgery after the achievement of a partial response (55%). Both these findings may be important in the multimodality approach to patients with lesions potenti ally resectable for cure. (C) 1999 Elsevier Science Ltd. All rights reserve d.