Front-line window therapy with temozolomide and irinotecan in patients with primary disseminated multifocal ewing sarcoma: Results of the isg/aieop ew-2 study

Purpose: The main objective was to evaluate the activity and tolerability of TEMIRI as a front-line treatment in primary disseminated Ewing sarcoma (PDMES) using the RECIST 1.1 criteria. The secondary objectives included the assessment of toxicity and the performance status/symptom changes. Methods: Between 2012 and 2018, patients with PDMES received two courses of temozolomide 100 mg/sqm/day + irinotecan 50 mg/sqm/day for 5 days every 3 weeks as an amendment to the Italian Sarcoma Group/Associazione Italiana EmatoIogia ed Oncologia Pediatrica (ISG/AIEOP) EW-2 protocol (EUDRACT#2009-012353-37, Vers. 1.02). Results: Thirty-four patients were enrolled. The median age at diagnosis was 19 years (range 3–55). After TEMIRI, the RECIST response was as follows: a partial response in 20 (59%) patients, stable disease in 11 (32%), and disease progression in 3 (9%). The ECOG/Lansky score was improved in 25/34 (73.5%) cases, and a reduction or disappearance of pain was observed in 31/34 patients (91%). The incidence of grade 3–4 toxicity was 3%. The 3-year event-free survival (EFS) and overall survival (OS) were 21% (95% CI 6–35%) and 36% (95% CI: 18–54%), respectively. Conclusion: the smooth handling and encouraging activity demonstrated by up-front TEMIRI did not change the EFS in PDMES, so this result suggests the need for the further evaluation of the efficacy of TEMIRI in combination with conventional treatments in non-metastatic patients.