title: A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  This phase I/II study examined the safety and efficacy of Sepantronium Bromide (S), a small-molecule selective survivin suppressant, administered in combination with carboplatin (C) and paclitaxel (P).
  
  
  METHODS
  Forty-one patients were treated on study. Twenty-two patients received escalating doses of S (3.6-12 mg/m(2)) and 19 with untreated stage IV non-small-cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10 mg/m(2) in combination with standard doses of C (AUC6) and P (200 mg/m(2)) for six cycles. S was administered as a continuous intravenous infusion (CIVI) over 72 h in 21-day treatment cycles. Study end points included safety and toxic effect, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates.
  
  
  RESULTS
  Treatment with S was well tolerated, and toxic effects were mostly hematological in the phase II study. Two (11%) partial responses were observed with a median PFS of 5.7 months and median OS 16.1 months. Pharmacodynamic analysis did not demonstrate an association with response.
  
  
  CONCLUSIONS
  The combination of S (10 mg/m(2)/day 72-h CIVI) administered with C and P every 3 weeks exhibited a favorable safety profile but failed to demonstrate an improvement in response rate in advanced NSCLC.
  
  
  BACKGROUND
  NCT01100931.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kelly
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: A
authors.initials: A
authors.lastname: Rajan
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: G
authors.initials: G
authors.lastname: Chun
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Chavez
authors.affiliation: Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda.
authors.forename: E
authors.initials: E
authors.lastname: Szabo
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: S
authors.initials: S
authors.lastname: Spencer
authors.affiliation: Medical Oncology, Walter Reed National Military Medical Center, Bethesda.
authors.forename: C A
authors.initials: CA
authors.lastname: Carter
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: U
authors.initials: U
authors.lastname: Guha
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: S
authors.initials: S
authors.lastname: Khozin
authors.affiliation: Astellas Pharma Global Development, Northbrook.
authors.forename: S
authors.initials: S
authors.lastname: Poondru
authors.affiliation: Astellas Pharma Global Development, Northbrook.
authors.forename: C
authors.initials: C
authors.lastname: Van Sant
authors.affiliation: Astellas Pharma Global Development, Northbrook.
authors.forename: A
authors.initials: A
authors.lastname: Keating
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Medical Oncology Branch, Center for Cancer Research.
authors.forename: W
authors.initials: W
authors.lastname: Figg
authors.affiliation: Medical Oncology Branch, Center for Cancer Research. Electronic address: giacconeg@mail.nih.gov.
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D013534:Survival; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; D016190:Carboplatin; D017239:Paclitaxel; C523798:sepantronium
keywords: apoptosis; non-small-cell lung cancer; sepantronium bromide; survivin