Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.
Summary of "Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies."
PURPOSE:
The primary objective of this study was to access the potential effects of trabectedin on the QT/QTc interval in patients with locally advanced or metastatic solid tumors.
METHODS:
Patients (n = 75) who had received ≤3 previous lines of chemotherapy and had either relapsed or had progressive disease were enrolled. Patients were administered 3-h intravenous infusions of placebo (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial triplicate ECG recordings and pharmacokinetic blood samples were collected over 24 h on both days. Heart rate corrected mean QT intervals and changes from predose baseline in QTc (ΔQTc) were assessed. The difference in ΔQTc between trabectedin and placebo was calculated at each time point (ΔΔQTc).
RESULTS:
The upper limits of the 90% confidence interval for ΔΔQTcF and ΔΔQTcB at all time points were less than the prespecified noninferiority margin of 10 ms (≤6.65 ms). No patient had a QTc > 500 ms or a time-matched increase from baseline in QTc > 60 ms at any time point. Regression analyses indicated ΔΔQTc was poorly correlated with trabectedin concentration. No adverse events suggestive of proarrhythmic potential were reported.
CONCLUSION:
Trabectedin did not prolong the QTc interval. Safety and pharmacokinetic profiles of trabectedin were similar to that observed in other ovarian and breast cancer studies.
Affiliation
Cancer Centers of North Carolina-Asheville, 20 Medical Park Drive, Asheville, NC, 28803, USA, raymond.thertulien@usoncology.com.
Journal Details
This article was published in the following journal.
Name: Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21739119
- DOI: http://dx.doi.org/10.1007/s00280-011-1697-6
Medical and Biotech [MESH] Definitions
Analgesia, Patient-controlled
Relief of PAIN, without loss of CONSCIOUSNESS, through ANALGESIC AGENTS administered by the patients. It has been used successfully to control POSTOPERATIVE PAIN, during OBSTETRIC LABOR, after BURNS, and in TERMINAL CARE. The choice of agent, dose, and lockout interval greatly influence effectiveness. The potential for overdose can be minimized by combining small bolus doses with a mandatory interval between successive doses (lockout interval).
Survival Rate
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Krukenberg Tumor
Mucocellular carcinoma of the ovary, usually metastatic from the gastrointestinal tract, characterized by areas of mucoid degeneration and the presence of signet-ring-like cells. It accounts for 30%-40% of metastatic cancers to the ovaries and possibly 1%-2% of all malignant ovarian tumors. The lesions may not be discovered until the primary disease is advanced, and most patients die of their disease within a year. In some cases, a primary tumor is not found. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1685)
Carcinoma, Ehrlich Tumor
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
Graft Vs Tumor Effect
Immunological rejection of tumor tissue/cells following bone marrow transplantation.
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