title: Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy.
abstract: BACKGROUND
  TZT-1027, a novel chemotherapeutic agent, is derived from dolastatin 10, and blocks cells during G2/M-phase by interfering with microtubule assembly and stability. TZT-1027 has exhibited potential cytotoxic activity in several human cancer cell lines (in vitro) and also demonstrated antitumor activity in human xenografts (in vivo). In addition, Phase I clinical investigations suggested activity in STS (soft-tissue sarcoma).
  
  
  METHODS
  Eligible patients were those who had histologic evidence of locally advanced or metastatic STS and who had received 1 prior treatment regimen with an anthracycline-based chemotherapy for metastatic disease. Subjects received intravenous infusions of TZT-1027 over 1 hour on Day 1 and Day 8 of each 21-day treatment course. Efficacy was evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  
  
  RESULTS
  Twenty-nine patients were enrolled and 28 patients received at least 1 course of study drug and were eligible for efficacy and safety evaluation. The median age of the patients was 48 years (range, 23-73 years) and the median baseline Eastern Cooperative Oncology Group (ECOG) performance status was 1 (range, 0-2). A total of 67 courses (range, 1-9 courses; median, 2 courses) of TZT-1027 were administered. No patient in the study demonstrated an objective response to treatment. Of 6 patients (21.4%) who experienced disease stabilization, 1 continued to have stable disease for 9.3 months. The median time to tumor progression was 44 days (95% confidence interval [95% CI], 43.0-54.0) and the median survival was 178 days (95% CI, 134.0-317.0). The most commonly reported toxicities were neutropenia, fatigue, and constipation.
  
  
  CONCLUSIONS
  TZT-1027 was found to be safe and well tolerated, and the hematologic toxicities observed were consistent with preclinical toxicology and Phase I study findings. No confirmed responses were seen in the current study.
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. spatel@mdanderson.org
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.forename: Mary Louise
authors.initials: ML
authors.lastname: Keohan
authors.forename: M Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: Daniel
authors.initials: D
authors.lastname: Rushing
authors.forename: Luis
authors.initials: L
authors.lastname: Baez
authors.forename: Kevie
authors.initials: K
authors.lastname: Feit
authors.forename: Robert
authors.initials: R
authors.lastname: DeJager
authors.forename: Sibyl
authors.initials: S
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D003248:Constipation / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy*
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D009842:Oligopeptides; C105791:soblidotin