caa a22 4500 605491569 CHVBK 20210128100510.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10147-015-0820-9 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0820-9 Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer [Elektronische Daten] [Masahiro Nozawa, Hirofumi Mukai, Shunji Takahashi, Hiroji Uemura, Takeo Kosaka, Yusuke Onozawa, Jun Miyazaki, Kazuhiro Suzuki, 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, Yoshiyuki Kakehi] 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 3weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25mg/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 3.68months (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. Japan Society of Clinical Oncology, 2015 Adverse event nationallicence Cabazitaxel nationallicence Japan nationallicence Neutropenia nationallicence Phase I nationallicence Prostate cancer nationallicence Nozawa Masahiro Department of Urology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan aut Mukai Hirofumi National Cancer Center Hospital East, Kashiwa, Chiba, Japan aut Takahashi Shunji Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan aut Uemura Hiroji Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan aut Kosaka Takeo Department of Urology, Keio University School of Medicine, Minato, Tokyo, Japan aut Onozawa Yusuke Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan aut Miyazaki Jun Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki Prefecture, Japan aut Suzuki Kazuhiro Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan aut Okihara Koji Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Japan aut Arai Yoichi Tohoku University Hospital, Aoba-ku, Sendai City, Miyagi, Japan aut Kamba Tomomi Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan aut Kato Masashi Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan aut Nakai Yasutomo Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan aut Furuse Hiroshi Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan aut Kume Haruki The University of Tokyo Hospital, Tokyo, Japan aut Ide Hisamitsu Teikyo University Hospital, Itabashi, Tokyo, Japan aut Kitamura Hiroshi Sapporo Medical University Hospital, Sapporo, Hokkaido, Japan aut Yokomizo Akira Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan aut Kimura Takahiro The Jikei University Hospital, Tokyo, Japan aut Tomita Yoshihiko Yamagata University Hospital, Yamagata, Japan aut Ohno Keiji Sanofi K.K., Tokyo, Japan aut Kakehi Yoshiyuki Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan aut International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 1026-1034 1341-9625 20:5<1026 2015 20 10147 https://doi.org/10.1007/s10147-015-0820-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0820-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nozawa Masahiro Department of Urology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan aut NATIONALLICENCE 700 1- Mukai Hirofumi National Cancer Center Hospital East, Kashiwa, Chiba, Japan aut NATIONALLICENCE 700 1- Takahashi Shunji Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan aut NATIONALLICENCE 700 1- Uemura Hiroji Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan aut NATIONALLICENCE 700 1- Kosaka Takeo Department of Urology, Keio University School of Medicine, Minato, Tokyo, Japan aut NATIONALLICENCE 700 1- Onozawa Yusuke Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan aut NATIONALLICENCE 700 1- Miyazaki Jun Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki Prefecture, Japan aut NATIONALLICENCE 700 1- Suzuki Kazuhiro Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan aut NATIONALLICENCE 700 1- Okihara Koji Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Japan aut NATIONALLICENCE 700 1- Arai Yoichi Tohoku University Hospital, Aoba-ku, Sendai City, Miyagi, Japan aut NATIONALLICENCE 700 1- Kamba Tomomi Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan aut NATIONALLICENCE 700 1- Kato Masashi Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan aut NATIONALLICENCE 700 1- Nakai Yasutomo Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan aut NATIONALLICENCE 700 1- Furuse Hiroshi Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan aut NATIONALLICENCE 700 1- Kume Haruki The University of Tokyo Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Ide Hisamitsu Teikyo University Hospital, Itabashi, Tokyo, Japan aut NATIONALLICENCE 700 1- Kitamura Hiroshi Sapporo Medical University Hospital, Sapporo, Hokkaido, Japan aut NATIONALLICENCE 700 1- Yokomizo Akira Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kimura Takahiro The Jikei University Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Tomita Yoshihiko Yamagata University Hospital, Yamagata, Japan aut NATIONALLICENCE 700 1- Ohno Keiji Sanofi K.K., Tokyo, Japan aut NATIONALLICENCE 700 1- Kakehi Yoshiyuki Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 1026-1034 1341-9625 20:5<1026 2015 20 10147