Trabectedin–irinotecan as a potential therapeutic option in desmoplastic small round cell tumor: A small case series

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive mesenchymal malignancy driven by the EWS–WT1 gene fusion. Prognosis remains poor despite intensive multimodal therapy. Preclinical studies indicate that trabectedin combined with irinotecan exerts synergistic antitumor effects in translocation-driven sarcomas.

We report a case series of eight young patients (age range 11-23 years) with advanced and relapsed DSRCT treated between 2021 and 2024 at five Italian pediatric oncology centers. The trabectedin-irinotecan combination (given on compassionate grounds) was administered as second-line therapy in six cases, and third-line in two. The regimen included trabectedin at 1.3 mg/m², 24-hour infusion, day 1, and irinotecan at 20 mg/m², days 8–12. Observed outcomes included: one complete remission, three partial responses, two minor responses, one mixed response, one progressive disease. The chemotherapy combination was overall well tolerated, with good preservation of patients’ quality of life, and no life-threatening adverse events reported.

This descriptive case series of trabectedin–irinotecan in DSRCT supports preclinical evidence of synergistic activity. The regimen was well tolerated and showed potential clinical benefit even in heavily pre-treated patients, providing a rationale for further studies to optimize dosing and explore early integration.