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.
| Original language | English |
|---|---|
| Pages (from-to) | 427-433 |
| Number of pages | 7 |
| Journal | Journal of Thoracic Oncology |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 2012 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Oncology
- Pulmonary and Respiratory Medicine
Cite this
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.
In: Journal of Thoracic Oncology, Vol. 7, No. 2, 01.01.2012, p. 427-433.Research output: Contribution to journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=84858334676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858334676&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e318238154d
DO - 10.1097/JTO.0b013e318238154d
M3 - Article
C2 - 22071785
AN - SCOPUS:84858334676
VL - 7
SP - 427
EP - 433
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 2
ER -