Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate

Akira Sawaki, Yasuhide Yamada, Yoshito Komatsu, Tatsuo Kanda, Toshihiko Doi, Masato Koseki, Hideo Baba, Yu Nien Sun, Koji Murakami, Toshirou Nishida

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. Methods: All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3). Results: Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported. Conclusions: One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.

Original languageEnglish
Pages (from-to)961-967
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume65
Issue number5
DOIs
Publication statusPublished - 2010 Apr
Externally publishedYes

Fingerprint

Gastrointestinal Stromal Tumors
Tumors
Toxicity
Proto-Oncogene Proteins c-kit
Platelet-Derived Growth Factor Receptors
Terminology
Safety
Antineoplastic Agents
imetelstat
Imatinib Mesylate
Fatigue of materials
Disease-Free Survival
Fatigue
Anemia
Diarrhea
Hypertension
Recurrence

Keywords

  • Angiogenesis inhibitor
  • Gastrointestinal stromal tumor (GIST)
  • Motesanib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. / Sawaki, Akira; Yamada, Yasuhide; Komatsu, Yoshito; Kanda, Tatsuo; Doi, Toshihiko; Koseki, Masato; Baba, Hideo; Sun, Yu Nien; Murakami, Koji; Nishida, Toshirou.

In: Cancer Chemotherapy and Pharmacology, Vol. 65, No. 5, 04.2010, p. 961-967.

Research output: Contribution to journalArticle

Sawaki, A, Yamada, Y, Komatsu, Y, Kanda, T, Doi, T, Koseki, M, Baba, H, Sun, YN, Murakami, K & Nishida, T 2010, 'Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate', Cancer Chemotherapy and Pharmacology, vol. 65, no. 5, pp. 961-967. https://doi.org/10.1007/s00280-009-1103-9
Sawaki, Akira ; Yamada, Yasuhide ; Komatsu, Yoshito ; Kanda, Tatsuo ; Doi, Toshihiko ; Koseki, Masato ; Baba, Hideo ; Sun, Yu Nien ; Murakami, Koji ; Nishida, Toshirou. / Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. In: Cancer Chemotherapy and Pharmacology. 2010 ; Vol. 65, No. 5. pp. 961-967.
@article{e7d6dedf02e74bcfbbde0b7fa4fae717,
title = "Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate",
abstract = "Purpose: Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. Methods: All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3). Results: Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported. Conclusions: One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.",
keywords = "Angiogenesis inhibitor, Gastrointestinal stromal tumor (GIST), Motesanib",
author = "Akira Sawaki and Yasuhide Yamada and Yoshito Komatsu and Tatsuo Kanda and Toshihiko Doi and Masato Koseki and Hideo Baba and Sun, {Yu Nien} and Koji Murakami and Toshirou Nishida",
year = "2010",
month = "4",
doi = "10.1007/s00280-009-1103-9",
language = "English",
volume = "65",
pages = "961--967",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate

AU - Sawaki, Akira

AU - Yamada, Yasuhide

AU - Komatsu, Yoshito

AU - Kanda, Tatsuo

AU - Doi, Toshihiko

AU - Koseki, Masato

AU - Baba, Hideo

AU - Sun, Yu Nien

AU - Murakami, Koji

AU - Nishida, Toshirou

PY - 2010/4

Y1 - 2010/4

N2 - Purpose: Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. Methods: All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3). Results: Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported. Conclusions: One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.

AB - Purpose: Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. Methods: All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3). Results: Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported. Conclusions: One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.

KW - Angiogenesis inhibitor

KW - Gastrointestinal stromal tumor (GIST)

KW - Motesanib

UR - http://www.scopus.com/inward/record.url?scp=77649186041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649186041&partnerID=8YFLogxK

U2 - 10.1007/s00280-009-1103-9

DO - 10.1007/s00280-009-1103-9

M3 - Article

VL - 65

SP - 961

EP - 967

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 5

ER -