title: A randomised, open-label, phase II study of neo/adjuvant doxorubicin and ifosfamide versus gemcitabine and docetaxel in patients with localised, high-risk, soft tissue sarcoma.
abstract: BACKGROUND
  Doxorubicin and ifosfamide (AI) is standard therapy for high-risk soft tissue sarcoma (STS) but often causes severe toxicities resulting in hospitalisation. Gemcitabine and docetaxel (GD) has efficacy in metastatic STS and may be better tolerated. We conducted a study to compare toxicities and efficacies of these regimens.
  
  
  METHODS
  This open-label, phase II, single institution trial randomised 80 patients with localised, resectable, high grade STS ⩾ 5 cm to either neo/adjuvant AI or GD. AI was doxorubicin (75 mg/m(2)) and ifosfamide (2.5 g/m(2)/d) on days 1-3 with mesna 500 mg/m(2)/dose. GD was gemcitabine 900 mg/m(2) on days 1, 8 and docetaxel 100mg/m(2) day 8. Both arms included filgrastim. The primary end-point was hospitalisation rate. Secondary end-points included disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  Between November 2004 and August 2012, 80 evaluable patients were randomised, 37 to AI and 43 to GT. In the AI arm, 13/37 (35%) patients were hospitalised versus 11/43 (26%) in the GD arm (p=0.25). Hospitalisation rates were not significantly different after adjusting for age, gender, location, chemotherapy and number of cycles (p=0.17). The 2-year and median DFS in the AI arm were 57% and 37 months, respectively, and 74% and not yet reached, respectively, in the GD arm. The most common serious adverse events with AI were haematologic. Metabolic derangements and constitutional symptoms were most common with GD.
  
  
  CONCLUSIONS
  Hospitalisation rate was less with GD but not statistically significant. There was a trend towards longer DFS with GD, and the regimen was tolerable, suggesting GD merits further study.
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Davis
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chugh
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Lucas
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: J Sybil
authors.initials: JS
authors.lastname: Biermann
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Wong
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Jon
authors.initials: J
authors.lastname: Jacobson
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Laurie
authors.initials: L
authors.lastname: Zyczynski
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Reinke
authors.affiliation: Clinical Trials Office, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States.
authors.forename: Gino
authors.initials: G
authors.lastname: Metko
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States. Electronic address: scotschu@med.umich.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006760:Hospitalization; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008824:Michigan; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D004317:Doxorubicin; D007069:Ifosfamide; D000093542:Gemcitabine
keywords: Docetaxel; Doxorubicin; Gemcitabine; Ifosfamide; Neo(adjuvant) chemotherapy; Soft tissue sarcoma