Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer

Isamu Okamoto, Hiroshige Yoshioka, Koji Takeda, Miyako Satouchi, Nobuyuki Yamamoto, Takashi Seto, Kazuo Kasahara, Masaki Miyazaki, Ryuichi Kitamura, Akio Ohyama, Noriko Hokoda, Hiroshi Nakayama, Eiji Yoshihara, Kazuhiko Nakagawa

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Introduction: TSU-68 is an oral small-molecule inhibitor that targets vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer. Methods: Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6mg · min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results: Thirty-seven patients were enrolled at the two dose levels of TSU-68. No dose-limiting toxicities were observed with TSU-68 at the 200 mg twice a day dose level. At 400 mg twice a day, one of six patients experienced a dose-limiting toxicity (anorexia of grade 3) during the first cycle. The 400 mg twice a day dose level was determined to be the recommended dose, and a total of 34 patients were treated at this dose. Overall, adverse events were mild to moderate in severity, with the most frequently observed such events being myelosuppression, neuropathy, and gastrointestinal disorders. No drug-related bleeding was observed. The objective response rate was 39.4% (95% confidence interval, 22.9-57.9%), and median progression-free survival was 5.6 months (95% confidence interval, 3.6-7.2 months). Coadministration of TSU-68, carboplatin, and paclitaxel had no substantial impact on the pharmacokinetics of these drugs. Conclusions: TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity.

元の言語英語
ページ(範囲)427-433
ページ数7
ジャーナルJournal of Thoracic Oncology
7
発行部数2
DOI
出版物ステータス出版済み - 1 1 2012
外部発表Yes

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Angiogenesis Inhibitors
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Drug Therapy
Receptor, Fibroblast Growth Factor, Type 1
Confidence Intervals
Platelet-Derived Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor-2
Anorexia
5-((1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-propanoic acid
Clinical Studies
Pharmaceutical Preparations
Disease-Free Survival
Area Under Curve
Pharmacokinetics
Hemorrhage

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

これを引用

Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer. / Okamoto, Isamu; Yoshioka, Hiroshige; Takeda, Koji; Satouchi, Miyako; Yamamoto, Nobuyuki; Seto, Takashi; Kasahara, Kazuo; Miyazaki, Masaki; Kitamura, Ryuichi; Ohyama, Akio; Hokoda, Noriko; Nakayama, Hiroshi; Yoshihara, Eiji; Nakagawa, Kazuhiko.

:: Journal of Thoracic Oncology, 巻 7, 番号 2, 01.01.2012, p. 427-433.

研究成果: ジャーナルへの寄稿記事

Okamoto, I, Yoshioka, H, Takeda, K, Satouchi, M, Yamamoto, N, Seto, T, Kasahara, K, Miyazaki, M, Kitamura, R, Ohyama, A, Hokoda, N, Nakayama, H, Yoshihara, E & Nakagawa, K 2012, 'Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer', Journal of Thoracic Oncology, 巻. 7, 番号 2, pp. 427-433. https://doi.org/10.1097/JTO.0b013e318238154d
Okamoto, Isamu ; Yoshioka, Hiroshige ; Takeda, Koji ; Satouchi, Miyako ; Yamamoto, Nobuyuki ; Seto, Takashi ; Kasahara, Kazuo ; Miyazaki, Masaki ; Kitamura, Ryuichi ; Ohyama, Akio ; Hokoda, Noriko ; Nakayama, Hiroshi ; Yoshihara, Eiji ; Nakagawa, Kazuhiko. / Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer. :: Journal of Thoracic Oncology. 2012 ; 巻 7, 番号 2. pp. 427-433.
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abstract = "Introduction: TSU-68 is an oral small-molecule inhibitor that targets vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer. Methods: Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6mg · min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results: Thirty-seven patients were enrolled at the two dose levels of TSU-68. No dose-limiting toxicities were observed with TSU-68 at the 200 mg twice a day dose level. At 400 mg twice a day, one of six patients experienced a dose-limiting toxicity (anorexia of grade 3) during the first cycle. The 400 mg twice a day dose level was determined to be the recommended dose, and a total of 34 patients were treated at this dose. Overall, adverse events were mild to moderate in severity, with the most frequently observed such events being myelosuppression, neuropathy, and gastrointestinal disorders. No drug-related bleeding was observed. The objective response rate was 39.4{\%} (95{\%} confidence interval, 22.9-57.9{\%}), and median progression-free survival was 5.6 months (95{\%} confidence interval, 3.6-7.2 months). Coadministration of TSU-68, carboplatin, and paclitaxel had no substantial impact on the pharmacokinetics of these drugs. Conclusions: TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity.",
author = "Isamu Okamoto and Hiroshige Yoshioka and Koji Takeda and Miyako Satouchi and Nobuyuki Yamamoto and Takashi Seto and Kazuo Kasahara and Masaki Miyazaki and Ryuichi Kitamura and Akio Ohyama and Noriko Hokoda and Hiroshi Nakayama and Eiji Yoshihara and Kazuhiko Nakagawa",
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T1 - Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer

AU - Okamoto, Isamu

AU - Yoshioka, Hiroshige

AU - Takeda, Koji

AU - Satouchi, Miyako

AU - Yamamoto, Nobuyuki

AU - Seto, Takashi

AU - Kasahara, Kazuo

AU - Miyazaki, Masaki

AU - Kitamura, Ryuichi

AU - Ohyama, Akio

AU - Hokoda, Noriko

AU - Nakayama, Hiroshi

AU - Yoshihara, Eiji

AU - Nakagawa, Kazuhiko

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Introduction: TSU-68 is an oral small-molecule inhibitor that targets vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer. Methods: Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6mg · min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results: Thirty-seven patients were enrolled at the two dose levels of TSU-68. No dose-limiting toxicities were observed with TSU-68 at the 200 mg twice a day dose level. At 400 mg twice a day, one of six patients experienced a dose-limiting toxicity (anorexia of grade 3) during the first cycle. The 400 mg twice a day dose level was determined to be the recommended dose, and a total of 34 patients were treated at this dose. Overall, adverse events were mild to moderate in severity, with the most frequently observed such events being myelosuppression, neuropathy, and gastrointestinal disorders. No drug-related bleeding was observed. The objective response rate was 39.4% (95% confidence interval, 22.9-57.9%), and median progression-free survival was 5.6 months (95% confidence interval, 3.6-7.2 months). Coadministration of TSU-68, carboplatin, and paclitaxel had no substantial impact on the pharmacokinetics of these drugs. Conclusions: TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity.

AB - Introduction: TSU-68 is an oral small-molecule inhibitor that targets vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer. Methods: Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6mg · min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results: Thirty-seven patients were enrolled at the two dose levels of TSU-68. No dose-limiting toxicities were observed with TSU-68 at the 200 mg twice a day dose level. At 400 mg twice a day, one of six patients experienced a dose-limiting toxicity (anorexia of grade 3) during the first cycle. The 400 mg twice a day dose level was determined to be the recommended dose, and a total of 34 patients were treated at this dose. Overall, adverse events were mild to moderate in severity, with the most frequently observed such events being myelosuppression, neuropathy, and gastrointestinal disorders. No drug-related bleeding was observed. The objective response rate was 39.4% (95% confidence interval, 22.9-57.9%), and median progression-free survival was 5.6 months (95% confidence interval, 3.6-7.2 months). Coadministration of TSU-68, carboplatin, and paclitaxel had no substantial impact on the pharmacokinetics of these drugs. Conclusions: TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity.

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