Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline

Randomized phase II multicenter trial

Sung Bae Kim, Changhoon Yoo, Jungsil Ro, Seock Ah Im, Young Hyuck Im, Jee Hyun Kim, Jin Hee Ahn, Kyung Hae Jung, Hong Suk Song, Seok Yun Kang, Hee Sook Park, Hyuncheol Chung

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m 2 on day 1 every 3 weeks, or docetaxel 60 mg/m 2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI] = 5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI = 4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI = 0.6-1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 % CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.

Original languageEnglish
Pages (from-to)753-761
Number of pages9
JournalInvestigational New Drugs
Volume32
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1

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docetaxel
Angiogenesis Inhibitors
Anthracyclines
Multicenter Studies
Breast Neoplasms
Confidence Intervals
Disease-Free Survival
5-((1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-propanoic acid

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Kim, Sung Bae ; Yoo, Changhoon ; Ro, Jungsil ; Im, Seock Ah ; Im, Young Hyuck ; Kim, Jee Hyun ; Ahn, Jin Hee ; Jung, Kyung Hae ; Song, Hong Suk ; Kang, Seok Yun ; Park, Hee Sook ; Chung, Hyuncheol. / Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline : Randomized phase II multicenter trial. In: Investigational New Drugs. 2014 ; Vol. 32, No. 4. pp. 753-761.
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title = "Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: Randomized phase II multicenter trial",
abstract = "The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m 2 on day 1 every 3 weeks, or docetaxel 60 mg/m 2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 {\%} confidence interval [CI] = 5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 {\%} CI = 4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 {\%} CI = 0.6-1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 {\%} CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.",
author = "Kim, {Sung Bae} and Changhoon Yoo and Jungsil Ro and Im, {Seock Ah} and Im, {Young Hyuck} and Kim, {Jee Hyun} and Ahn, {Jin Hee} and Jung, {Kyung Hae} and Song, {Hong Suk} and Kang, {Seok Yun} and Park, {Hee Sook} and Hyuncheol Chung",
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Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline : Randomized phase II multicenter trial. / Kim, Sung Bae; Yoo, Changhoon; Ro, Jungsil; Im, Seock Ah; Im, Young Hyuck; Kim, Jee Hyun; Ahn, Jin Hee; Jung, Kyung Hae; Song, Hong Suk; Kang, Seok Yun; Park, Hee Sook; Chung, Hyuncheol.

In: Investigational New Drugs, Vol. 32, No. 4, 01.01.2014, p. 753-761.

Research output: Contribution to journalArticle

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T1 - Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline

T2 - Randomized phase II multicenter trial

AU - Kim, Sung Bae

AU - Yoo, Changhoon

AU - Ro, Jungsil

AU - Im, Seock Ah

AU - Im, Young Hyuck

AU - Kim, Jee Hyun

AU - Ahn, Jin Hee

AU - Jung, Kyung Hae

AU - Song, Hong Suk

AU - Kang, Seok Yun

AU - Park, Hee Sook

AU - Chung, Hyuncheol

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m 2 on day 1 every 3 weeks, or docetaxel 60 mg/m 2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI] = 5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI = 4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI = 0.6-1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 % CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.

AB - The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m 2 on day 1 every 3 weeks, or docetaxel 60 mg/m 2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI] = 5.4-12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI = 4.0-13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI = 0.6-1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 % CI = 0.1-0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.

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