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Phase II study of intravenous TZT‐1027 in patients with advanced or metastatic soft‐tissue sarcomas with prior exposure to anthracycline‐based chemotherapy
Author(s) -
Patel Shreyaskumar,
Keohan Mary Louise,
Saif M. Wasif,
Rushing Daniel,
Baez Luis,
Feit Kevie,
DeJager Robert,
Anderson Sibyl
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22334
Subject(s) - medicine , anthracycline , chemotherapy , soft tissue sarcoma , phases of clinical research , sarcoma , cancer , response evaluation criteria in solid tumors , regimen , metastatic breast cancer , surgery , performance status , chemotherapy regimen , oncology , soft tissue , breast cancer , pathology
BACKGROUND. TZT‐1027, a novel chemotherapeutic agent, is derived from dolastatin 10, and blocks cells during G 2 /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.