Sequential dose-dense doxorubicin and ifosfamide in advanced soft-tissue sarcoma patients in an out-patient-basis schedule

Abstract

Aims. This phase II study explored activity/safety of front-line dose-dense chemotherapy in high-grade STS (soft tissue sarcoma) patients and tested ezrin as prognostic factor. Patients and Methods. The protocol consisted of three cycles of doxorubicin (DOXO) 30mg/m2 on days 1-3 every 2 weeks, followed by three cycles of ifosfamide (IFO) 2.5g/m2 two hours a day on days 1-5 every 3 weeks, with GCSF support. Ezrin was assessed immunohistochemically. Results. Twenty patients, 13 metastatic and 7 locally advanced, were enrolled. Median age was 39 years (25-60). Median dose intensities were 42mg/m2/week and 3.6g/m2/week for DOXO and IFO, respectively. Grade 3/4 toxicities occurred in 18 patients. Response rate was 15 (3 of 20) by RECIST. Patients younger than 45 years with locally advanced disease and synovial histology presented longer survival. A trend towards longer survival was observed among ezrin-positive patients. Conclusions. This dose-dense schedule should not be routinely used due to its high frequency of toxic events; however, a sequential strategy with DOXO and IFO may benefit selected patients and should be further explored with lower doses. The role of ezrin as a prognostic marker should be confirmed in a larger group of patients. Copyright © 2011 G. F. G. Almeida et al.