Phase <scp>II</scp> trial of aflibercept with <scp>FOLFIRI</scp> as a second‐line treatment for Japanese patients with metastatic colorectal cancer
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- Tadamichi Denda
- Department of Gastroenterology Chiba Cancer Center Chiba Japan
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- Daisuke Sakai
- Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine Suita Japan
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- Tetsuya Hamaguchi
- Department of Gastrointestinal Medical Oncology National Cancer Center Hospital Tokyo Japan
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- Naotoshi Sugimoto
- Department of Medical Oncology Osaka Medical Center for Cancer and Cardiovascular Disease Osaka Japan
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- Takashi Ura
- Department of Clinical Oncology Aichi Cancer Center Hospital Nagoya Japan
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- Kentaro Yamazaki
- Department of Gastrointestinal Oncology Shizuoka Cancer Center Shizuoka Japan
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- Hirofumi Fujii
- Department of Clinical Oncology Jichi Medical University Hospital Shimotsuke Japan
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- Takeshi Kajiwara
- Department of Gastrointestinal Medical Oncology Shikoku Cancer Center Matsuyama Japan
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- Takako Eguchi Nakajima
- Department of Medical Oncology St. Marianna University School of Medical Hospital Kawasaki Japan
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- Shin Takahashi
- Department of Medical Oncology Tohoku University Hospital Sendai Japan
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- Satoshi Otsu
- Department of Medical Oncology Oita University Hospital Yufu Japan
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- Yoshito Komatsu
- Department of Cancer Center Hokkaido University Hospital Sapporo Japan
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- Fumio Nagashima
- Department of Medical Oncology Kyorin University Hospital Mitaka Japan
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- Toshikazu Moriwaki
- Department of Gastroenterology University of Tsukuba Hospital Tsukuba Japan
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- Taito Esaki
- Department of Gastrointestinal and Medical Oncology National Kyushu Cancer Center Fukuoka Japan
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- Takeo Sato
- Department of Gastrointestinal Surgery Kitasato University East Hospital Sagamihara Japan
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- Michio Itabashi
- Department of Surgery 2 Tokyo Women's Medical University Hospital Tokyo Japan
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- Eiji Oki
- Department of Gastrointestinal Surgery Kyushu University Hospital Fukuoka Japan
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- Toru Sasaki
- Local Medical Operation Sanofi K. K. Tokyo Japan
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- Yoshinori Sunaga
- Biostatstics& Programming Sanofi K. K. Tokyo Japan
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- Samira Ziti‐Ljajic
- Pharmacokinetics Sanofi Oncology Alfortville France
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- Claire Brillac
- Modeling& Simulation Sanofi Oncology Alfortville France
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- Takayuki Yoshino
- Department of Gastrointestinal Oncology National Cancer Center Hospital East Kashiwa Japan
Description
<jats:p>Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (<jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content>) as a second‐line treatment for metastatic colorectal cancer (<jats:styled-content style="fixed-case">mCRC</jats:styled-content>) in Japanese patients. Aflibercept (4 mg/kg) plus <jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content> was administered every 2 weeks in 62 patients with <jats:styled-content style="fixed-case">mCRC</jats:styled-content> until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (<jats:styled-content style="fixed-case">ORR</jats:styled-content>); secondary endpoints were progression‐free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5‐fluorouracil. A total of 60 patients were evaluated for <jats:styled-content style="fixed-case">ORR</jats:styled-content>; 50 had received prior bevacizumab. The <jats:styled-content style="fixed-case">ORR</jats:styled-content> was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (<jats:styled-content style="fixed-case">DCR</jats:styled-content>) was 80.0% (69.9%‐90.1%). The median progression‐free survival was 5.42 months (4.14‐6.70 months) and the median overall survival was 15.59 months (11.20‐19.81 months). No treatment‐related deaths were observed, and no significant drug‐drug interactions were found. The most common treatment‐emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/<jats:styled-content style="fixed-case">mL</jats:styled-content> (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5‐fluorouracil: The clearance was 11.1 L/h/m<jats:sup>2</jats:sup> (28%) for irinotecan and, at steady state, 72.6 L/h/m<jats:sup>2</jats:sup> (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to <jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content> was shown to be beneficial and well‐tolerated in Japanese patients with <jats:styled-content style="fixed-case">mCRC</jats:styled-content>. ClinicalTrials.gov Identifier: <jats:styled-content style="fixed-case">NCT</jats:styled-content>01882868.</jats:p>
Journal
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- Cancer Science
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Cancer Science 110 (3), 1032-1043, 2019-02-22
Wiley
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Details 詳細情報について
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- CRID
- 1360848660420766336
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- ISSN
- 13497006
- 13479032
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- Data Source
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- Crossref
- KAKEN