title: Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database.
abstract: BACKGROUND
  Although sarcomas account for only 1% of all solid tumours, patients with sarcomas comprise a larger proportion of patients entering phase I trials, due to the limited number of registered or active drugs for these diseases. To help in patient selection, we evaluated the utility of the predictive Royal Marsden Score which had been derived in carcinoma patients. In addition, we analysed efficacy and toxicity regarding the sarcoma population enrolled in phase I trials.
  
  
  METHODS
  We used data from a European Database comprising 2182 patients treated in phase I trials in 14 European institutions between 2005 and 2007.
  
  
  RESULTS
  One hundred and seventy-eight patients diagnosed with advanced sarcoma or other mesenchymal tumours were identified and accounted for 217 phase I trial participations during the study period. Histological type, class of drug, number of metastatic sites, high serum lactate dehydrogenase activity (LDH), low albumin and high white blood cell count were independent prognostic factors. Poor performance status (PS), liver metastases and high leucocyte count were associated with increased risk of early death. The class of drug used was the strongest predictor of progression-free survival (PFS) duration, inhibitors of angiogenesis and histone deacetylase giving the best results. Poor PS, high serum LDH and low lymphocyte count correlated with shorter PFS. In this heterogeneous population, PFS with investigational agents appeared comparable with that previously published for patients receiving standard treatments beyond first line.
  
  
  CONCLUSIONS
  Prognostic factors in sarcoma patients do not differ from a broader phase I population. Efficacy measures suggest that some patients with sarcoma derive benefit from therapy in this setting which could therefore be considered for patients with no remaining standard therapeutic option.
authors.affiliation: Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, Sutton The Institute of Cancer Research, Sutton, UK Departments of Medical Oncology cassierp@hotmail.com.
authors.forename: P A
authors.initials: PA
authors.lastname: Cassier
authors.affiliation: Biostatistics, Centre Léon Bérard, Lyon.
authors.forename: V
authors.initials: V
authors.lastname: Polivka
authors.affiliation: Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, Sutton The Institute of Cancer Research, Sutton, UK.
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: J-C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Department of General Cancer, Centre Oscar Lambret, Lille, France.
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.affiliation: Southern Europe New Drug Organization Foundation, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marsoni
authors.affiliation: Erasmus University Medical Center, Cancer Institute, Rotterdam.
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Research Unit for Molecular Therapy of Cancer, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Morales-Barrera
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: C
authors.initials: C
authors.lastname: Gomez-Roca
authors.affiliation: The Beatson West of UK Cancer Centre, Glasgow.
authors.forename: T R J
authors.initials: TR
authors.lastname: Evans
authors.affiliation: Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: R
authors.initials: R
authors.lastname: Plummer
authors.affiliation: Department of Oncology, Istituto Oncologico Della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Gallerani
authors.affiliation: Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, Sutton The Institute of Cancer Research, Sutton, UK.
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.affiliation: Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, Sutton The Institute of Cancer Research, Sutton, UK.
authors.forename: D
authors.initials: D
authors.lastname: Olmos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D016208:Databases, Factual; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: clinical trial; phase I; sarcoma; targeted therapies