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

Authors

  • Shreyaskumar Patel MD,

    Corresponding author
    1. Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Room FC11-3000, Houston, TX 77030
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    • Fax: (713) 794-1934

  • Mary Louise Keohan MD,

    1. Department of Sarcoma, Columbia Presbyterian Medical Center, New York, New York
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  • M. Wasif Saif MD,

    1. Department of Medical Oncology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Daniel Rushing MD,

    1. Department of Hematology Oncology, Indiana University, Indianapolis, Indiana
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  • Luis Baez MD,

    1. Department of Hematology Oncology, San Juan Veterans Affairs Medical Center, San Juan, Puerto Rico
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  • Kevie Feit MPA,

    1. Department of Oncology, Daiichi Medical Research, Park Ridge, New Jersey
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    • Drs. Feit and De Jager were employed by Daiichi Medical Research during the time this study was performed.

  • Robert DeJager MD,

    1. Department of Oncology, Daiichi Medical Research, Park Ridge, New Jersey
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    • Drs. Feit and De Jager were employed by Daiichi Medical Research during the time this study was performed.

  • Sibyl Anderson MD

    1. Department of Medicine, Developmental Chemotherapy Services, Memorial Sloan-Kettering Cancer Center, New York, New York
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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.

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