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Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer

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Abstract

Background

We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study.

Methods

Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m2 we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response.

Results

In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35–4.63).

Conclusions

In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

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Acknowledgments

The authors would like to thank all patients who participated in the study, and Efficacy and Safety Evaluation Committee members Dr Koichiro Akakura and Dr Toshihiko Doi for their support. Dr Paul Scutt of MediTech Media provided editorial support in the form of medical writing services. This study was funded by Sanofi.

Conflict of interest

Hirofumi Mukai has received research funding from Sanofi; Shunji Takahashi has received lecture fees from Astra Zeneca, Novartis, Astellas and Daiichi-Sankyo, and research funding from Sanofi, Taiho, Zenyaku, Nippon Boehringer, Chugai and Novartis; Kazuhiro Suzuki has received lecture fees and honoraria for writing promotional material from Sanofi; Masahiro Nozawa, Hiroji Uemura, Takeo Kosaka, Yusuke Onozawa, Jun Miyazaki, Koji Okihara, Yoichi Arai, Tomomi Kamba, Masashi Kato, Yasutomo Nakai, Hiroshi Furuse, Haruki Kume, Hisamitsu Ide, Hiroshi Kitamura, Akira Yokomizo, Takahiro Kimura, Yoshihiko Tomita, Keiji Ohno and Yoshiyuki Kakehi have no conflicts of interest.

Author information

Author notes

  1. Yasutomo Nakai

    Present address: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

  2. Yoshihiko Tomita

    Present address: Niigata University, Niigata, Japan

Authors and Affiliations

  1. Department of Urology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Masahiro Nozawa

  2. National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Hirofumi Mukai

  3. Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan

    Shunji Takahashi

  4. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Hiroji Uemura

  5. Department of Urology, Keio University School of Medicine, Minato, Tokyo, Japan

    Takeo Kosaka

  6. Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Yusuke Onozawa

  7. Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki Prefecture, Japan

    Jun Miyazaki

  8. Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Kazuhiro Suzuki

  9. Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Japan

    Koji Okihara

  10. Tohoku University Hospital, Aoba-ku, Sendai City, Miyagi, Japan

    Yoichi Arai

  11. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Tomomi Kamba

  12. Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masashi Kato

  13. Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan

    Yasutomo Nakai

  14. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    Hiroshi Furuse

  15. The University of Tokyo Hospital, Tokyo, Japan

    Haruki Kume

  16. Teikyo University Hospital, Itabashi, Tokyo, Japan

    Hisamitsu Ide

  17. Sapporo Medical University Hospital, Sapporo, Hokkaido, Japan

    Hiroshi Kitamura

  18. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Akira Yokomizo

  19. The Jikei University Hospital, Tokyo, Japan

    Takahiro Kimura

  20. Yamagata University Hospital, Yamagata, Japan

    Yoshihiko Tomita

  21. Sanofi K.K., Tokyo, Japan

    Keiji Ohno

  22. Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan

    Yoshiyuki Kakehi

Authors
  1. Masahiro Nozawa
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  2. Hirofumi Mukai
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  3. Shunji Takahashi
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  4. Hiroji Uemura
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  5. Takeo Kosaka
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  6. Yusuke Onozawa
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  7. Jun Miyazaki
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  8. Kazuhiro Suzuki
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  9. Koji Okihara
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  10. Yoichi Arai
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  11. Tomomi Kamba
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  12. Masashi Kato
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  13. Yasutomo Nakai
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  14. Hiroshi Furuse
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  15. Haruki Kume
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  16. Hisamitsu Ide
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  17. Hiroshi Kitamura
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  18. Akira Yokomizo
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  19. Takahiro Kimura
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  20. Yoshihiko Tomita
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  21. Keiji Ohno
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  22. Yoshiyuki Kakehi
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Corresponding author

Correspondence to Masahiro Nozawa.

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Nozawa, M., Mukai, H., Takahashi, S. et al. Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer. Int J Clin Oncol 20, 1026–1034 (2015). https://doi.org/10.1007/s10147-015-0820-9

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  • DOI: https://doi.org/10.1007/s10147-015-0820-9

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