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Keywords:

  • TZT-1027;
  • Phase II study;
  • metastatic soft-tissue sarcoma;
  • response;
  • toxicity evaluation

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. Cancer 2006. © 2006 American Cancer Society.