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

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 TomitaKeiji Ohno, Yoshiyuki Kakehi

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1026-1034
Number of pages9
JournalInternational Journal of Clinical Oncology
Volume20
Issue number5
DOIs
Publication statusPublished - 2015 Mar 26

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Castration
Prostatic Neoplasms
docetaxel
Neutropenia
Febrile Neutropenia
Granulocyte Colony-Stimulating Factor
Prostate-Specific Antigen
Maximum Tolerated Dose
Population
Macrophage Colony-Stimulating Factor
cabazitaxel
Prednisolone
Nausea
Fatigue
Diarrhea
Cohort Studies
Therapeutics
Pharmacokinetics
Confidence Intervals
Safety

Keywords

  • Adverse event
  • Cabazitaxel
  • Japan
  • Neutropenia
  • Phase I
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Surgery
  • Hematology

Cite this

Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer. / Nozawa, Masahiro; Mukai, Hirofumi; Takahashi, Shunji; Uemura, Hiroji; Kosaka, Takeo; Onozawa, Yusuke; Miyazaki, Jun; Suzuki, Kazuhiro; Okihara, Koji; Arai, Yoichi; Kamba, Tomomi; Kato, Masashi; Nakai, Yasutomo; Furuse, Hiroshi; Kume, Haruki; Ide, Hisamitsu; Kitamura, Hiroshi; Yokomizo, Akira; Kimura, Takahiro; Tomita, Yoshihiko; Ohno, Keiji; Kakehi, Yoshiyuki.

In: International Journal of Clinical Oncology, Vol. 20, No. 5, 26.03.2015, p. 1026-1034.

Research output: Contribution to journalArticle

Nozawa, M, Mukai, H, Takahashi, S, Uemura, H, Kosaka, T, Onozawa, Y, Miyazaki, J, Suzuki, K, Okihara, K, Arai, Y, Kamba, T, Kato, M, Nakai, Y, Furuse, H, Kume, H, Ide, H, Kitamura, H, Yokomizo, A, Kimura, T, Tomita, Y, Ohno, K & Kakehi, Y 2015, 'Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer', International Journal of Clinical Oncology, vol. 20, no. 5, pp. 1026-1034. https://doi.org/10.1007/s10147-015-0820-9
Nozawa, Masahiro ; Mukai, Hirofumi ; Takahashi, Shunji ; Uemura, Hiroji ; Kosaka, Takeo ; Onozawa, Yusuke ; Miyazaki, Jun ; Suzuki, Kazuhiro ; Okihara, Koji ; Arai, Yoichi ; Kamba, Tomomi ; Kato, Masashi ; Nakai, Yasutomo ; Furuse, Hiroshi ; Kume, Haruki ; Ide, Hisamitsu ; Kitamura, Hiroshi ; Yokomizo, Akira ; Kimura, Takahiro ; Tomita, Yoshihiko ; Ohno, Keiji ; Kakehi, Yoshiyuki. / Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer. In: International Journal of Clinical Oncology. 2015 ; Vol. 20, No. 5. pp. 1026-1034.
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T1 - Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer

AU - Nozawa, Masahiro

AU - Mukai, Hirofumi

AU - Takahashi, Shunji

AU - Uemura, Hiroji

AU - Kosaka, Takeo

AU - Onozawa, Yusuke

AU - Miyazaki, Jun

AU - Suzuki, Kazuhiro

AU - Okihara, Koji

AU - Arai, Yoichi

AU - Kamba, Tomomi

AU - Kato, Masashi

AU - Nakai, Yasutomo

AU - Furuse, Hiroshi

AU - Kume, Haruki

AU - Ide, Hisamitsu

AU - Kitamura, Hiroshi

AU - Yokomizo, Akira

AU - Kimura, Takahiro

AU - Tomita, Yoshihiko

AU - Ohno, Keiji

AU - Kakehi, Yoshiyuki

PY - 2015/3/26

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N2 - 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.

AB - 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.

KW - Adverse event

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KW - Neutropenia

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