A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma

Kanai, Fumihiko; Yoshida, Haruhiko; Tateishi, Ryosuke; Sato, Shinpei; Kawabe, Takao; Obi, Shuntaro; Kondo, Yuji; Taniguchi, Makoto; Tagawa, Kunio; Ikeda, Masafumi; Morizane, Chigusa; Okusaka, Takuji; Arioka, Hitoshi; Shiina, Shuichiro; Omata, Masao

doi:10.1007/s00280-010-1320-2

Cited by 85 publications

(60 citation statements)

References 26 publications

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“…TSU-68, a tyrosine kinase inhibitor of PDGFR, FGFR and VEGFR, has revealed promising preliminary efficacy in a phase Ⅰ/Ⅱ trial of heavily pretreated advanced HCC patients, with a 13.1 mo OS and 2.1 mo TTP [40] . Another trial combining TSU-68 with TACE in patients with advanced HCC showed a trend towards prolonged PFS; however, this observation was not statistically significant [41] .…”

Section: Other Antiangiogenic Therapiesmentioning

confidence: 99%

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

Deng

Zeng

Shen

2015

WJH

143

121

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Section: Other Antiangiogenic Therapiesmentioning

confidence: 99%

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

Deng

Zeng

Shen

2015

WJH

143

121

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“…9,10 Our choice of TTP as study endpoint was based on the recommendation of an expert panel convened by the American Association for the Study of Liver Diseases. 11 The median time to tumor progression in this study was 12 weeks (range 4-32) (Figure 1(c)).…”

Section: Efficacymentioning

confidence: 99%

A phase II study of TRC105 in patients with hepatocellular carcinoma who have progressed on sorafenib

et al. 2015

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Background: Endoglin is an endothelial cell membrane receptor essential for angiogenesis and highly expressed on the vasculature of many tumor types, including hepatocellular carcinoma (HCC). TRC105 is a chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis, and complements VEGF inhibitors. Objective: The aim of this phase II study was to evaluate the efficacy of anti-endoglin therapy with TRC105 in patients with advanced HCC, post-sorafenib. Methods: Patients with HCC and compensated liver function (Childs-Pugh A/B7), ECOG 0/1, were enrolled to a single-arm, phase II study of TRC105 15 mg/kg IV every two weeks. Patients must have progressed on or been intolerant of prior sorafenib. A Simon optimal two-stage design was employed with a 50% four-month PFS target for progression to the second stage. Correlative biomarkers evaluated included DCE-MRI as well as plasma levels of angiogenic biomarkers and soluble CD105. Results: A total accrual of 27 patients was planned. However, because of lack of efficacy and in accordance with the Simon two-stage design, 11 patients were enrolled. There were no grade 3/4 treatment-related toxicities. Most frequent toxicities were headache (G2; N ¼ 3) and epistaxis (G1; N ¼ 4). One patient had a confirmed partial response by standard RECIST criteria and biologic response on DCE-MRI but the four-month PFS was insufficient to proceed to the second stage of the study. Conclusions: TRC105 was well tolerated in this HCC population following sorafenib. Although there was evidence of clinical activity, this did not meet prespecified criteria to proceed to the second stage. TRC105 development in HCC continues as combination therapy with sorafenib.

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“…In a Phase I/II trial, Kanai et al reported an overall response rate of 51% with 2.9% complete response, 5.7% partial response and 42.8% stable disease. The median TTP was 2.1 months and median OS was 13.1 months [44]. Adverse events include diarrhea, malaise, and ALT / AST elevation, and were similar to other TKIs.…”

Section: Other Anti-angiogenic Agentsmentioning

confidence: 91%

Systemic Management of Advanced Hepatocellular Carcinoma Patients: The Role of Multi-Targeted Anti-Angiogenic Inhibitors

Chiu¹,

Pang²,

Poon³

et al. 2012

Hepatocellular Carcinoma - Clinical Research

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A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma

Abstract: TSU-68 at a dose of 200 mg bid determined by stratification into liver function, showed promising preliminary efficacy with a high safety profile in patients with HCC who had been heavily pre-treated.

Cited by 85 publications

References 26 publications

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

A phase II study of TRC105 in patients with hepatocellular carcinoma who have progressed on sorafenib

Systemic Management of Advanced Hepatocellular Carcinoma Patients: The Role of Multi-Targeted Anti-Angiogenic Inhibitors

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