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A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA)

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Abstract

Purpose

This Phase I dose-escalation study (GASTANA) evaluated the safety, tolerability, pharmacokinetics and preliminary antitumor activity of cabazitaxel in Asian patients with advanced gastric adenocarcinoma failing two prior chemotherapy regimens.

Methods

Cabazitaxel safety/tolerability was determined using a standard 3 + 3 dose-escalation design based on dose-limiting toxicities (DLTs) in Cycle 1. Three dose levels (DL) were planned: 20, 25 and 15 mg/m2 (DL 1, DL 2 and DL −1).

Results

Fifteen patients were evaluable for DLTs. At DL 1, no DLTs occurred in three patients. At DL 2, four patients were enrolled (one patient discontinued), with only one DLT observed [Grade 4 febrile neutropenia (FN)]; however, all four patients experienced FN, hence three more patients were enrolled at DL 1 who experienced two DLTs (Grade 4 neutropenia >7 days). In response, DL −1 was opened, with no DLTs observed in six patients. In the total population (n = 16), frequent Grade 3/4 toxicities included neutropenia (63 %) and FN (38 %), best overall responses included one partial response (6.3 %; DL −1) and eight stable disease (50 %), and median progression-free survival was 83 days.

Conclusions

No unexpected safety findings were observed. Significant toxicities included neutropenia and FN, potentially due to patients being heavily pretreated and the accumulated toxicity of prior taxane therapy.

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Acknowledgments

This study was funded by Sanofi. The authors received editorial support from Paul Scutt of MediTech Media Ltd, funded by Sanofi. This study was funded by Sanofi.

Conflict of interest

Yoon-Koo Kang has a consultancy/advisory role with Sanofi, Roche, Daiho and Novartis and has received funding from Sanofi, Roche, Jeil, Novartis and Bayer. Lin Shen has received remuneration from Roche, Novartis and Amgen, funding from Celgene, Taiho, Heng Rui, Sanofi and Roche, and has a consultant/advisory role with Roche and Novartis. Yu Zhou, Jooyun Lee and Chenlu Wei are employees of Sanofi. Baek-Yeol Ryoo, Shinkyo Yoon and Min-Hee Ryu have no conflicts to disclose.

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Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea

    Yoon-Koo Kang, Baek-Yeol Ryoo, Shinkyo Yoon & Min-Hee Ryu

  2. Department of GI Oncology, Peking University Cancer Hospital and Institute, Beijing, China

    Lin Shen

  3. Sanofi, 235 Banpo-daero, Seocho-gu, Seoul, 137-804, Korea

    Jooyun Lee

  4. Sanofi, HP Plaza, No.112, Jian Guo Road, Chaoyang District, Beijing, 100022, China

    Chenlu Wei

  5. Sanofi, Kerry Center, 1228 Middle Yan’an Road, Jing An District, Shanghai, 200040, China

    Yu Zhou

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  1. Yoon-Koo Kang
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Correspondence to Yoon-Koo Kang.

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Kang, YK., Ryoo, BY., Yoon, S. et al. A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA). Cancer Chemother Pharmacol 75, 309–318 (2015). https://doi.org/10.1007/s00280-014-2638-y

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  • DOI: https://doi.org/10.1007/s00280-014-2638-y

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