A Randomized, Double-blind, Placebo-controlled Study to Assess QTc Interval Prolongation of Standard Dose Aflibercept in Cancer Patients Treated With Docetaxel

3033 Background: QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods: We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥ 450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥ 500 ms, rate of increase of the QTc interval by ≥ 60 ms, and the development of complications (VT, TdP and SCD). Results: In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥ 500 ms was documented in 53 (18.3%) and QTc progression ≥ 60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Conclusions: The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. [Table: see text]

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Droperidol and Ondansetron-induced QT Interval Prolongation

Anesthesiology ◽

10.1097/aln.0b013e31817fd8c8 ◽

2008 ◽

Vol 109 (2) ◽

pp. 206-212 ◽

Cited By ~ 80

Author(s):

Beny Charbit ◽

Jean Claude Alvarez ◽

Eric Dasque ◽

Emuri Abe ◽

Jean Louis Démolis ◽

...

Keyword(s):

Qt Interval ◽

Plasma Concentrations ◽

Postoperative Nausea And Vomiting ◽

Pharmacokinetic Interaction ◽

Controlled Study ◽

Qtc Interval ◽

Interval Prolongation ◽

Double Blind ◽

Qt Interval Prolongation ◽

Controlled Conditions

Background Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has never been confirmed and compared with both drugs under controlled conditions. The objective was to study the effects of droperidol and ondansetron alone or in combination on QT interval duration in healthy subjects. Methods Sixteen healthy volunteers, eight males and eight females, were enrolled in this prospective, double-blind, randomized, placebo-controlled study. Subjects received 1 mg droperidol, 4 mg ondansetron, 1 mg droperidol plus 4 mg ondansetron, or a placebo, intravenously in a crossover design. Fridericia-corrected QT interval (QTcF) and plasma concentrations were measured repeatedly during 10 h at each study period. The primary endpoint was the maximal placebo time-matched and baseline-subtracted QTcF prolongation (DeltaDeltaQTcF). Results Compared with placebo, both droperidol and ondansetron significantly prolonged the QTcF interval. DeltaDeltaQTcF prolongation was 25 +/- 8 ms after droperidol, significantly greater than the 17 +/- 10-ms prolongation with ondansetron (P = 0.014). The combination of droperidol and ondansetron significantly increased the mean maximal DeltaDeltaQTcF by 28 +/- 10 ms. The combination induced greater QTcF prolongation compared with ondansetron alone (P = 0.001), but not with droperidol alone (P = 0.33). There was no significant pharmacokinetic interaction between droperidol and ondansetron. Conclusions Under controlled conditions, both droperidol and ondansetron either alone or in combination induced significant marked QTc interval prolongation. However, the combination of both drugs did not significantly increase QTc prolongation compared with that induced by droperidol alone.

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The efficacy of oral melatonin in improving sleep in cancer patients with insomnia: A randomized double-blind placebo-controlled study

Indian Journal of Palliative Care ◽

10.4103/0973-1075.185039 ◽

2016 ◽

Vol 22 (3) ◽

pp. 295 ◽

Cited By ~ 9

Author(s):

MadhuriS Kurdi ◽

SindhuPriya Muthukalai

Keyword(s):

Cancer Patients ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Phase III randomised double-blind placebo controlled study of rofecoxib (VIOXX) in colorectal cancer patients following potentially curable therapy

http://isrctn.org/> ◽

10.1186/isrctn98278138 ◽

2013 ◽

Author(s):

David J Kerr

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Phase Iii ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo ◽

Colorectal Cancer Patients

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A Randomized, Double-Blind, Placebo-Controlled Study of Fentanyl Buccal Tablets for Breakthrough Pain: Efficacy and Safety in Japanese Cancer Patients

Journal of Pain and Symptom Management ◽

10.1016/j.jpainsymman.2013.07.006 ◽

2014 ◽

Vol 47 (6) ◽

pp. 990-1000 ◽

Cited By ~ 12

Author(s):

Toshifumi Kosugi ◽

Sasagu Hamada ◽

Chizuko Takigawa ◽

Katsunori Shinozaki ◽

Hiroshi Kunikane ◽

...

Keyword(s):

Cancer Patients ◽

Breakthrough Pain ◽

Controlled Study ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Buccal Tablets

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Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients

Journal of Hospital Infection ◽

10.1016/0195-6701(90)90025-j ◽

1990 ◽

Vol 15 (1) ◽

pp. 95-102 ◽

Cited By ~ 81

Author(s):

M Ranson

Keyword(s):

Central Venous Catheter ◽

Cancer Patients ◽

Venous Catheter ◽

Catheter Insertion ◽

Controlled Study ◽

Central Venous Catheter Insertion ◽

Central Venous ◽

Double Blind ◽

Double Blind Placebo

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Clinical Evaluation of Ramosetron Injections in the Treatment of Cisplatin-Induced Nausea and Vomiting

Journal of International Medical Research ◽

10.1177/147323000203000301 ◽

2002 ◽

Vol 30 (3) ◽

pp. 211-219 ◽

Cited By ~ 6

Author(s):

K Noda ◽

M Ikeda ◽

O Yoshida ◽

S Yano ◽

T Taguchi ◽

...

Keyword(s):

Cancer Patients ◽

Clinical Efficacy ◽

Clinical Evaluation ◽

Adverse Reactions ◽

Phase Iii ◽

Controlled Study ◽

Double Blind ◽

Safety And Efficacy ◽

Double Blind Placebo ◽

Efficacy Analysis

A phase III, double-blind, placebo-controlled study was performed to examine the safety and efficacy of ramosetron in cancer patients with cisplatin-induced nausea/vomiting. Patients were divided into two groups: group R received 0.3 mg ramosetron intravenously and group P received placebo. Eighty-eight patients were enrolled, 44 in each group; 84 (43 in group R, 41 in group P) were included in the clinical efficacy analysis and 86 (44 in group R, 42 in group P) in the safety analysis. Ramosetron was significantly more clinically effective than placebo against nausea, vomiting and anorexia; 65.1% of patients in group R experienced no vomiting in the first 6 h of observation compared with 7.3% of those receiving placebo. No serious adverse reactions or significant differences in safety were observed between the groups. Based on these results, ramosetron injection is effective in the treatment of cisplatin-induced nausea/vomiting and its clinical usefulness is demonstrated here.

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