Article

An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology, Springer Nature, ISSN 1432-0843

Volume 73, 6, 2014

DOI:10.1007/s00280-014-2460-6, Dimensions: pub.1027316192, PMID: 24718982,

Affiliations

Organisations

  1. (1) Cardiology Unit, Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Paris, France
  2. (2) Cancer Center of Kansas, grid.477024.2
  3. (3) California Pacific Medical Center, grid.17866.3e
  4. (4) Ghent University Hospital, grid.410566.0
  5. (5) University of California, San Diego, grid.266100.3
  6. (6) Rigshospitalet, grid.475435.4, Capital Region
  7. (7) Catholic University of Louvain, grid.7942.8
  8. (8) Purchase Cancer Group, Paducah, KY, USA
  9. (9) Huntsman Cancer Institute, grid.479969.c
  10. (10) Maastricht University Medical Centre, grid.412966.e
  11. (11) Uppsala University Hospital, grid.412354.5
  12. (12) Herlev Hospital, grid.411900.d, Capital Region
  13. (13) Kansas City VA Medical Center, grid.413849.3
  14. (14) Temple University, grid.264727.2
  15. (15) Sanofi (France), grid.417924.d
  16. (16) Sanofi (United States), grid.417555.7
  17. (17) Decatur Memorial Hospital, grid.433546.3

Description

PURPOSE: This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events. METHODS: Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. RESULTS: The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (-0.012 [95 % CI -0.017; -0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade ≥3 cardiac adverse events were observed; Grade ≥3 hypotension and lymphocele occurred in two patients and one patient, respectively. CONCLUSION: These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.

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2014: Unused

Research area: Medicine

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2014: Level 1

Research area: Medicine

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Times Cited: 1

Field Citation Ratio (FCR): 0.29

Relative Citation ratio (RCR): 0.04