title: Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy.
abstract: BACKGROUND
  The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials.
  
  
  METHODS
  This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials.
  
  
  RESULTS
  One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04).
  
  
  CONCLUSIONS
  A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.
authors.affiliation: Medical Oncology Department, Centre Oscar Lambret, Lille, France. Electronic address: n-penel@o-lambret.fr.
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.affiliation: Medical Oncology Department, Ludwig Center at Dana-Farber Cancer Institute, Boston, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Demetri
authors.affiliation: Medical Oncology Department, Centre Léon Bérard, Lyon, France.
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Medical Oncology Department, Centre Oscar Lambret, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Cousin
authors.affiliation: Medical Oncology Department,Mount Sinai School of Medicine, New York.
authors.forename: R G
authors.initials: RG
authors.lastname: Maki
authors.affiliation: Medical Oncology Department, Santa Monica Oncology Center Santa Monica, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Chawla
authors.affiliation: Medical Oncology Department, Royal Marsden Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.affiliation: Medical Oncology Department, Fox Chase Cancer Center, Philadelphia, USA.
authors.forename: M
authors.initials: M
authors.lastname: von Mehren
authors.affiliation: Medical Oncology Department, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: Medical Oncology Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.affiliation: Medical Oncology Department, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Casali
authors.affiliation: Medical Oncology Department, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.affiliation: Medical Oncology Department, Marien Hospital, Dûsseldorf, Deutschland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Schütte
authors.affiliation: Scientific liaison office, Novex Pharma, Levallois-Perret, France.
authors.forename: A
authors.initials: A
authors.lastname: Cassar
authors.affiliation: Statistics Department & Medical affairs, Pharmamar, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gomez
authors.affiliation: Statistics Department & Medical affairs, Pharmamar, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Statistics Department & Medical affairs, Pharmamar, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Zintl
authors.affiliation: Statistics Department & Medical affairs, Pharmamar, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pontes
authors.affiliation: Medical Oncology Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D004149:Dioxoles / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D004317:Doxorubicin; D000077606:Trabectedin