B Bui-Nguyen1, I Ray-Coquard2, C Chevreau3, N Penel4, J O Bay5, J M Coindre6, D Cupissol7, A Italiano8, F Bonichon9, J P Lotz10, A Thyss11, M Jimenez12, S Mathoulin-Pélissier9, J Y Blay2. 1. Department of Medical Oncology, Institut Bergonié, Bordeaux. Electronic address: bui@bergonie.org. 2. Center Léon Bérard, Lyon. 3. Institut Claudius Regaud, Toulouse. 4. Center Oscar Lambret, Lille. 5. Center Jean Perrin, Center Hospitalier Universitaire Estaing, Clermont-Ferrand. 6. Department of Pathology and INSERM U916, Institut Bergonié, Bordeaux. 7. Center Val d'Aurelle-Paul Lamarque, Montpellier. 8. Department of Medical Oncology, Institut Bergonié, Bordeaux. 9. Clinical and Epidemiological Research Unit, Institut Bergonié and Inserm CIC-EC 7, Bordeaux. 10. Hôpital Tenon, Paris. 11. Center Antoine-Lacassagne, Nice. 12. French National Federation for Comprehensive Cancer Centers, Paris, France.
Abstract
BACKGROUND: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-respondingpatients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS:From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.
RCT Entities:
BACKGROUND:Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.
Authors: Jörg Thomas Hartmann; M Horger; T Kluba; A Königsrainer; P de Zwart; C Hann von Weyhern; F Eckert; W Budach; C Bokemeyer Journal: Invest New Drugs Date: 2013-10-04 Impact factor: 3.850
Authors: William D Tap; Robin L Jones; Brian A Van Tine; Bartosz Chmielowski; Anthony D Elias; Douglas Adkins; Mark Agulnik; Matthew M Cooney; Michael B Livingston; Gregory Pennock; Meera R Hameed; Gaurav D Shah; Amy Qin; Ashwin Shahir; Damien M Cronier; Robert Ilaria; Ilaria Conti; Jan Cosaert; Gary K Schwartz Journal: Lancet Date: 2016-06-09 Impact factor: 79.321