Sebastian Dorin Asaftei1, Nadia Puma2, Anna Paioli3, Marco Petraz4, Carlo Morosi5, Marta Podda2, Angela Tamburini6, Emanuela Palmerini3, Luca Coccoli7, Giovanni Grignani8, Carla Manzitti9, Rossella Bertulli10, Francesco De Leonardis11, Marco Rabusin12, Anna Campello1, Elisa Tirtei1, Piero Picci13, Arcangelo Prete14, Alessandra Longhi3, Franca Fagioli1, Roberto Luksch2. 1. Pediatric Onco-Hematology, A.O.U Città della Salute e della Scienza, University of Turin, Piazza Polonia, 94, 10126 Turin, Italy. 2. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy. 3. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli, 1, 40136 Bologna, Italy. 4. Pediatric Radiology, A.O.U Città della Salute e della Scienza, Piazza Polonia, 94, 10126 Turin, Italy. 5. Radiology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy. 6. Pediatric Onco-Hematology Unit, Centro di Eccellenza di Oncologia ed Ematologia, AUOM, Viale Gaetano Pieraccini, 24, 50139 Florence, Italy. 7. Pediatric Hematology Oncology Unit, S. Chiara-Pisa University Hospital AOUP, Via Bonanno Pisano, 10, 56126 Pisa, Italy. 8. Department of Medical Oncology, Candiolo Cancer Institute FPO-IRCCS, SP 142, km 3,95, 10060 Candiolo, Italy. 9. Department of Haematology-Oncology, IRCCS G. Gaslini Children's Hospital, Via Gerolamo Gaslini, 3, 16147 Genoa, Italy. 10. Adult Mesenchymal Tumor Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy. 11. Division of Pediatric Haematology Oncology, University Hospital, Piazza Giulio Cesare, 11, 70124 Bari, Italy. 12. Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria, 65, 34137 Trieste, Italy. 13. Italian Sarcoma Group, Via Cà Ricchi, 33, 40068 San Lazzaro di Savena, Italy. 14. Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, Via Giuseppe Massarenti, 9, 40138 Bologna, Italy.
Abstract
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.
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.