Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy

Shreyaskumar Patel, Mary Louise Keohan, M. Wasif Saif, Daniel Rushing, Luis Baez, Kevie Feit, Robert DeJager, Sibyl Anderson

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50 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2881-2887
Number of pages7
JournalCancer
Volume107
Issue number12
DOIs
StatePublished - Dec 15 2006

Keywords

  • Metastatic soft-tissue sarcoma
  • Phase II study
  • Response
  • Toxicity evaluation
  • TZT-1027

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Patel, S., Keohan, M. L., Saif, M. W., Rushing, D., Baez, L., Feit, K., DeJager, R., & Anderson, S. (2006). Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy. Cancer, 107(12), 2881-2887. https://doi.org/10.1002/cncr.22334