Sequential Dose-Dense Doxorubicin and Ifosfamide in Advanced Soft-Tissue Sarcoma Patients in an Out-Patient-Basis Schedule

Abstract EN

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) 30 mg/m2 on days 1–3 every 2 weeks, followed by three cycles of ifosfamide (IFO) 2.5 g/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 42 mg/m2/week and 3.6 g/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.