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

Authors: Patel, S.; Keohan, M. L.; Saif, M. W.; Rushing, D.; Baez, L.; Feit, K.; DeJager, R.; Anderson, S.
Article 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. © 2006 American Cancer Society.
Keywords: adult; cancer chemotherapy; cancer survival; clinical article; treatment outcome; aged; middle aged; clinical trial; constipation; fatigue; neutropenia; advanced cancer; diarrhea; drug efficacy; monotherapy; antineoplastic agents; nuclear magnetic resonance imaging; follow up; antineoplastic agent; metastasis; computer assisted tomography; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; myalgia; drug dose escalation; dyspnea; sarcoma; multicenter study; response; limb pain; soft tissue sarcoma; injection site pain; thorax radiography; anthracycline derivative; anthracyclines; alopecia; oligopeptides; injections, intravenous; infusion pump; tzt-1027; auristatin pe; metastatic soft-tissue sarcoma; phase ii study; toxicity evaluation
Journal Title: Cancer
Volume: 107
Issue: 12
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2006-12-15
Start Page: 2881
End Page: 2887
Language: English
DOI: 10.1002/cncr.22334
PUBMED: 17109446
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 15" - "Export Date: 4 June 2012" - "CODEN: CANCA" - "Source: Scopus"
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