PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers receiveddoxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.
RCT Entities:
PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant humangranulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.
Authors: Jérôme Fayette; Nicolas Penel; Christine Chevreau; Jean-Yves Blay; Didier Cupissol; Antoine Thyss; Cécile Guillemet; Maria Rios; Frédéric Rolland; Pierre Fargeot; Jacques Olivier Bay; Simone Mathoulin-Pelissier; Jean Michel Coindre; Binh Bui-Nguyen Journal: Invest New Drugs Date: 2009-01-16 Impact factor: 3.850
Authors: Peter Reichardt; Karin Oechsle; Daniel Pink; Carsten Bokemeyer; F Schneller; Rolf Issels; Lothar Kanz; Jörg Thomas Hartmann Journal: Invest New Drugs Date: 2003-11 Impact factor: 3.850
Authors: G Huygh; Paul M J Clement; H Dumez; P Schöffski; H Wildiers; J Selleslach; J M Jimeno; I De Wever; R Sciot; L Duck; A T Van Oosterom Journal: Sarcoma Date: 2006-12-31
Authors: D Bafaloukos; C Papadimitriou; H Linardou; G Aravantinos; P Papakostas; D Skarlos; P Kosmidis; G Fountzilas; H Gogas; C Kalofonos; A M Dimopoulos Journal: Br J Cancer Date: 2004-11-01 Impact factor: 7.640