title: Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Beatson Oncology Centre, Western Infirmary, Glasgow, United Kingdom.
authors.forename: W P
authors.initials: WP
authors.lastname: Steward
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: R
authors.initials: R
authors.lastname: Somers
authors.forename: D
authors.initials: D
authors.lastname: Spooner
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.forename: M
authors.initials: M
authors.lastname: Clavel
authors.forename: D
authors.initials: D
authors.lastname: Crowther
authors.forename: J
authors.initials: J
authors.lastname: Rouesse
authors.forename: T
authors.initials: T
authors.lastname: Tursz
authors.forename: E
authors.initials: E
authors.lastname: Tueni
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide