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

Abstract

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.

• Authors: Pierre Maison-Blanche, Shaker Dakhil, Ari Baron, Sylvie Rottey, Fred Millard, Gedske Daugaard, Jean-Pascal Machiels, William Conkright, Sunil Sharma, Patricia M M B Soetekouw, Jeffrey Yachnin, Lisa Sengeløv, Peter Van Veldhuizen, Sanjiv S Agarwala, Dorothée Sémiond, Mustapha Chadjaa, Liji Shen, James L Wade
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 73 Issue 6 Pg. 1241-52 (Jun 2014) ISSN: 1432-0843 [Electronic] Germany
• PMID: 24718982 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Taxoids
• cabazitaxel

Topics

• Adult
• Aged
• Dose-Response Relationship, Drug
• Electrocardiography (drug effects)
• Female
• Heart (drug effects)
• Heart Rate (drug effects)
• Humans
• Male
• Middle Aged
• Neoplasms (drug therapy, pathology)
• Prospective Studies
• Taxoids (adverse effects, therapeutic use)