Perrine Marec-Berard1, Cécile Dalban2, Nathalie Gaspar3, Laurence Brugieres3, Jean-Claude Gentet4, Cyril Lervat5, Nadège Corradini6, Marie-Pierre Castex7, Claudine Schmitt8, Hélène Pacquement9, Marie-Dominique Tabone10, Mehdi Brahmi11, Séverine Metzger2, Jean-Yves Blay12, David Pérol2. 1. Paediatric Department, Hematology and Oncology Pediatric Institute, Centre Léon Bérard, Lyon, France. Electronic address: perrine.marec-berard@ihope.fr. 2. Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France. 3. Department of Pediatrics and Adolescents Oncology, Gustave Roussy, Villejuif, France. 4. Department of Pediatric Hematology and Oncology, La Timone Hospital, Marseille, France. 5. Department of Pediatric Oncology, Centre Oscar Lambret, Lille, France. 6. Department of Pediatric Hematology and Oncology, CHU Nantes, Nantes, France. 7. Paediatric Department, Hospital Centre, Toulouse, France. 8. Pediatric Hospital, CHU Nancy, Vandoeuvre-les-Nancy, France. 9. Pediatric Oncology Department, Institut Curie, Paris, France. 10. Department of Pediatric Hematology and Oncology, A.Trousseau Hospital, APHP, Paris, France. 11. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 12. Department of Medical Oncology & Claude Bernard University, Centre Léon Bérard, Lyon, France.
Abstract
BACKGROUND: The role of high-dose chemotherapy in relapsing osteosarcomas has not been established. We evaluated the efficacy and tolerance of high-dose thiotepa (HDTp) after standard chemotherapy (SCT) in patients with relapsed osteosarcoma. PATIENTS AND METHODS: This randomised open-label phase II study enrolled patients 1-50 years, with local or metastatic relapse of a high-grade osteosarcoma, not progressive after two cycles of SCT, for whom a complete surgery can be achievable following treatment. The trial assigned enrolled patients in a 1:1 ratio to receive two additional courses of SCT + HDTp and autologous transplantation (Arm A), or SCT alone (Arm B). Surgery for complete resection was scheduled as soon as feasible. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS) and safety. RESULTS:From September 2009 to November 2016, 44 patients were randomised (A:22; B:22). In total, 54.5% were males, and the median age was 16 years (9-32years). The two-year OS rate was 66.7% (95% CI 42.5-82.5) (SCT + HDTp, Arm A) versus 50.0% (95% CI 28.2-68.4) for SCT alone (Arm B). Median OS was 27.4 and 24.8 months, respectively (hazard ratio [HR] 0.826, 95% CI 0.393-1.734; p = 0.6123). Median PFS was 15.6 (8.9-24.9) months in Arm A versus 7.2 (4.8-33.3) months in Arm B, p = 0.3845. Among the 22 patients treated with SCT + HDTp, 16 (72.7%) experienced at least one grade ≥3 adverse events versus 18/22 (81.8%) patients treated with SCT. No toxic death occurred. CONCLUSION: Adjuvant HDTp failed to significantly improve OS and PFS in resectable relapsed osteosarcomas. Despite a trend of prolonged survival and an acceptable toxicity, thiotepa cannot be recommended. KEY MESSAGE: HDTp and autologous transplantation added to SCT did not improve OS and PFS in patients with resectable relapsed osteosarcomas. Despite a trend of prolonged survival, thiotepa cannot be recommended.
RCT Entities:
BACKGROUND: The role of high-dose chemotherapy in relapsing osteosarcomas has not been established. We evaluated the efficacy and tolerance of high-dose thiotepa (HDTp) after standard chemotherapy (SCT) in patients with relapsed osteosarcoma. PATIENTS AND METHODS: This randomised open-label phase II study enrolled patients 1-50 years, with local or metastatic relapse of a high-grade osteosarcoma, not progressive after two cycles of SCT, for whom a complete surgery can be achievable following treatment. The trial assigned enrolled patients in a 1:1 ratio to receive two additional courses of SCT + HDTp and autologous transplantation (Arm A), or SCT alone (Arm B). Surgery for complete resection was scheduled as soon as feasible. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS) and safety. RESULTS: From September 2009 to November 2016, 44 patients were randomised (A:22; B:22). In total, 54.5% were males, and the median age was 16 years (9-32years). The two-year OS rate was 66.7% (95% CI 42.5-82.5) (SCT + HDTp, Arm A) versus 50.0% (95% CI 28.2-68.4) for SCT alone (Arm B). Median OS was 27.4 and 24.8 months, respectively (hazard ratio [HR] 0.826, 95% CI 0.393-1.734; p = 0.6123). Median PFS was 15.6 (8.9-24.9) months in Arm A versus 7.2 (4.8-33.3) months in Arm B, p = 0.3845. Among the 22 patients treated with SCT + HDTp, 16 (72.7%) experienced at least one grade ≥3 adverse events versus 18/22 (81.8%) patients treated with SCT. No toxic death occurred. CONCLUSION: Adjuvant HDTp failed to significantly improve OS and PFS in resectable relapsed osteosarcomas. Despite a trend of prolonged survival and an acceptable toxicity, thiotepa cannot be recommended. KEY MESSAGE: HDTp and autologous transplantation added to SCT did not improve OS and PFS in patients with resectable relapsed osteosarcomas. Despite a trend of prolonged survival, thiotepa cannot be recommended.
Authors: J Asher Jenkins; Schelomo Marmor; Jane Yuet Ching Hui; Heather Beckwith; Anne H Blaes; David Potter; Todd M Tuttle Journal: Breast Cancer Res Treat Date: 2021-10-29 Impact factor: 4.872