title: Tasisulam sodium (LY573636 sodium) as third-line treatment in patients with unresectable, metastatic non-small-cell lung cancer: a phase-II study.
abstract: BACKGROUND
  Tasisulam sodium (hereafter referred to as tasisulam) is a novel anticancer compound that induces apoptosis and exhibits antiangiogenesis activity in a broad range of cancer models, including non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Tasisulam was administered as a 2-hour infusion every 21 days as third-line treatment in patients with advanced (stage IIIB/IV) NSCLC.
  
  
  RESULTS
  Thirty-two patients received a Cmax target dose of 420 µg/ml. Median time to progression was 3.12 months, median progression-free survival was 2.69 months, and median overall survival was 8.48 months. There were no objective responses; 43.8% of patients achieved stable disease. A high rate of grade-4 hematologic toxicity in the first 30 patients led to exploration of a lower Cmax target dose of 380 µg/ml. The rate of grade-4 hematologic toxicity (thrombocytopenia and/or neutropenia) at the 380-µg/ml dose (n = 20) was 20% versus 34% at the 420-µg/ml dose.
  
  
  CONCLUSIONS
  Tasisulam has only modest activity as a third-line treatment of patients with unresectable/metastatic NSCLC. The high rate of grade-4 hematologic toxicity observed with this highly albumin- bound compound in this patient population provided challenges for fixed Cmax-based dosing. Alternative dosing methods, including varying the Cmax target dose by predose albumin, are under investigation in other studies.
authors.affiliation: Department of Clinical & Biological Sciences, University of Torino, Orbassano (Torino), Italy. giorgio.scagliotti@unito.it
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Robert
authors.initials: R
authors.lastname: Ilaria
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: J
authors.initials: J
authors.lastname: von Pawel
authors.forename: Juergen R
authors.initials: JR
authors.lastname: Fischer
authors.forename: Sabine
authors.initials: S
authors.lastname: Ermisch
authors.forename: Dinesh P
authors.initials: DP
authors.lastname: de Alwis
authors.forename: Joan
authors.initials: J
authors.lastname: Andrews
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Lucio
authors.initials: L
authors.lastname: Crino
authors.forename: Corinna
authors.initials: C
authors.lastname: Eschbach
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D000075202:Contraindications; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011013:Pneumonectomy; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; C534068:N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide; D013449:Sulfonamides