Trabectedin plus radiotherapy well tolerated in patients with myxoid liposarcoma

A phase II nonrandomized trial of trabectedin in combination with radiotherapy for the treatment of myxoid liposarcoma has failed to meet its endpoint, although this treatment combination appears to be well tolerated in patients.

The trial included 46 patients with histologic, centrally reviewed diagnosis of localized resectable myxoid liposarcoma arising from an extremity or the trunk wall. All patients received trabectedin at the recommended dose identified in the phase I trial (1.5 mg/m²), with intravenous infusion during 24 hours every 21 days for a total of three cycles.

After completion of the first trabectedin infusion (cycle 1, day 2), the patients started radiotherapy (25 fractions of radiation for a total of 45 Gy). Surgery was scheduled 3–4 weeks after the administration of the last preoperative cycle and not until 4 weeks after the end of preoperative radiotherapy. Researchers mapped pathologic specimens in tumour sections to estimate the histologic changes and the percentage of viable tumour after neoadjuvant treatment.

The analysis included 42 patients (median age 43 years, 67 percent men), with one patient not available for centralized review by RECIST. The primary endpoint of overall response was not met. Only nine out of 41 patients (22 percent) achieved partial response with neoadjuvant treatment with trabectedin and radiotherapy, five out of 39 (13 percent) achieved a complete pathologic response, and 20 out of 39 (51 percent) had no more than 10 percent of a viable remaining tumour.

Over a median follow-up of 37 months, seven had disease recurrence. No deaths were recorded. The median time to recurrence was 15 months. The corresponding 4-year overall survival was 100 percent, while disease-free survival was 84 percent.

The major grade 3 and grade 4 toxic effects for the 46 patients were neutropenia (26.1 percent), leukopenia (4.3 percent), anaemia (2.2 percent), alanine aminotransferase level elevation (21.7 percent), aspartate aminotransferase level elevation (13.1 percent), and gamma-glutamyl transferase level elevation (10.9 percent). There were no treatment-related deaths.