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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

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Anthracyclines
Sarcoma
Drug Therapy
dolastatin 10
Confidence Intervals
G2 Phase
Constipation
Neutropenia
Heterografts
Intravenous Infusions
Human Activities
Microtubules
Cell Division
Toxicology
Fatigue
soblidotin
Neoplasms
Therapeutics
Safety
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy. / Patel, Shreyaskumar; Keohan, Mary Louise; Saif, M. Wasif; Rushing, Daniel; Baez, Luis; Feit, Kevie; DeJager, Robert; Anderson, Sibyl.

In: Cancer, Vol. 107, No. 12, 15.12.2006, p. 2881-2887.

Research output: Contribution to journalArticle

Patel, S, Keohan, ML, Saif, MW, 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, vol. 107, no. 12, pp. 2881-2887. https://doi.org/10.1002/cncr.22334
Patel, Shreyaskumar ; Keohan, Mary Louise ; Saif, M. Wasif ; Rushing, Daniel ; Baez, Luis ; Feit, Kevie ; DeJager, Robert ; Anderson, Sibyl. / Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy. In: Cancer. 2006 ; Vol. 107, No. 12. pp. 2881-2887.
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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.",
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T1 - Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy

AU - Patel, Shreyaskumar

AU - Keohan, Mary Louise

AU - Saif, M. Wasif

AU - Rushing, Daniel

AU - Baez, Luis

AU - Feit, Kevie

AU - DeJager, Robert

AU - Anderson, Sibyl

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N2 - 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.

AB - 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.

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KW - Toxicity evaluation

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