title: Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer.
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/m(2) 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.
authors: Department of Urology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan. nozawa06@med.kindai.ac.jp.
authors: Masahiro
authors: M
authors: Nozawa
authors: National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Hirofumi
authors: H
authors: Mukai
authors: Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan.
authors: Shunji
authors: S
authors: Takahashi
authors: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Hiroji
authors: H
authors: Uemura
authors: Department of Urology, Keio University School of Medicine, Minato, Tokyo, Japan.
authors: Takeo
authors: T
authors: Kosaka
authors: Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Yusuke
authors: Y
authors: Onozawa
authors: Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki Prefecture, Japan.
authors: Jun
authors: J
authors: Miyazaki
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Kazuhiro
authors: K
authors: Suzuki
authors: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Japan.
authors: Koji
authors: K
authors: Okihara
authors: Tohoku University Hospital, Aoba-ku, Sendai City, Miyagi, Japan.
authors: Yoichi
authors: Y
authors: Arai
authors: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Tomomi
authors: T
authors: Kamba
authors: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Masashi
authors: M
authors: Kato
authors: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.|Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Yasutomo
authors: Y
authors: Nakai
authors: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors: Hiroshi
authors: H
authors: Furuse
authors: The University of Tokyo Hospital, Tokyo, Japan.
authors: Haruki
authors: H
authors: Kume
authors: Teikyo University Hospital, Itabashi, Tokyo, Japan.
authors: Hisamitsu
authors: H
authors: Ide
authors: Sapporo Medical University Hospital, Sapporo, Hokkaido, Japan.
authors: Hiroshi
authors: H
authors: Kitamura
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Akira
authors: A
authors: Yokomizo
authors: The Jikei University Hospital, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Kimura
authors: Yamagata University Hospital, Yamagata, Japan.|Niigata University, Niigata, Japan.
authors: Yoshihiko
authors: Y
authors: Tomita
authors: Sanofi K.K., Tokyo, Japan.
authors: Keiji
authors: K
authors: Ohno
authors: Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors: Yoshiyuki
authors: Y
authors: Kakehi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000628:therapy; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel
keywords: Adverse event; Cabazitaxel; Japan; Neutropenia; Phase I; Prostate cancer