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) 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.

Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis

“…STS is a rare and diverse solid tumor that originates from mesenchymal precursors. STSs account for about 1% of all new adult malignancies (32). Doxorubicin, either alone or in combination with other chemotherapy, remains a standard treatment.…”

“…Doxorubicin, either alone or in combination with other chemotherapy, remains a standard treatment. However, the survival time of patients with metastatic diseases is only 12-16 months, and the 2-year survival rate is only about 30% (32,33).…”