scholarly journals The Risk of QTc Prolongation in Non-Diabetic and Diabetic Patients Taking Tyrosine Kinase Inhibitors (TKIs)- A Patient Safety Project at a Private Oncology Practice

2021 ◽  
Vol 11 (6) ◽  
pp. 799-807
Author(s):  
Zhongju Lu ◽  
Ying Luu ◽  
Jack Ip ◽  
Imran Husain ◽  
Michael Lu ◽  
...  
Keyword(s):  
Patient Safety ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Diabetic Patients ◽  
Qtc Prolongation ◽  
Oncology Practice

scholarly journals Risk of QTc prolongation among cancer patients treated with tyrosine kinase inhibitors

2020 ◽  
Vol 147 (11) ◽  
pp. 3160-3167 ◽  
Author(s):  
Anan A. Abu Rmilah ◽  
Grace Lin ◽  
Kebede H. Begna ◽  
Paul A. Friedman ◽  
Joerg Herrmann
Keyword(s):  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Qtc Prolongation

scholarly journals Differential Inhibitory Actions of Multitargeted Tyrosine Kinase Inhibitors on Different Ionic Current Types in Cardiomyocytes

2020 ◽  
Vol 21 (5) ◽  
pp. 1672 ◽  
Author(s):  
Wei-Ting Chang ◽  
Ping-Yen Liu ◽  
Kaisen Lee ◽  
Yin-Hsun Feng ◽  
Sheng-Nan Wu
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Ionic Current ◽  
Small Animal ◽  
Ionic Currents ◽  
Neonatal Rat ◽  
Delayed Rectifier ◽  
Qtc Prolongation ◽  
The Impact

Lapatinib (LAP) and sorafenib (SOR) are multitargeted tyrosine kinase inhibitors (TKIs) with antineoplastic properties. In clinical observations, LAP and SOR may contribute to QTc prolongation, but the detailed mechanism for this has been largely unexplored. In this study, we investigated whether LAP and SOR affect the activities of membrane ion channels. Using a small animal model and primary cardiomyocytes, we studied the impact of LAP and SOR on Na+ and K+ currents. We found that LAP-induced QTc prolongation in mice was reversed by isoproterenol. LAP or SOR suppressed the amplitude of the slowly activating delayed-rectifier K+ current (IK(S)) in H9c2 cells in a time- and concentration-dependent fashion. The LAP-mediated inhibition of IK(S) was reversed by adding isoproterenol or meclofenamic acid, but not by adding diazoxide. The steady-state activation curve of IK(S) during exposure to LAP or SOR was shifted toward a less negative potential, with no change in the gating charge required to activate the current. LAP shortened the recovery from IK(S) deactivation. As rapid repetitive stimuli, the IK(S) amplitude decreased; however; the LAP-induced inhibition of IK(S) remained effective. LAP or SOR alone also suppressed inwardly rectifying K+ and voltage-gated Na+ current in neonatal rat ventricular myocytes. The inhibition of ionic currents during exposure to TKIs could be an important mechanism underlying changes in QTc intervals.

Risk of QTc interval prolongation among cancer patients treated with tyrosine kinase inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3033-3033
Author(s):  
Anan Abdelmoti Abu Rmilah ◽  
Grace Lin ◽  
Joerg Herrmann
Keyword(s):  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Complication Rates ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qtc Prolongation ◽  
Qtc Interval Prolongation ◽  
Life Threatening

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]

scholarly journals The Noninvestigational Use of Tyrosine Kinase Inhibitors in Thyroid Cancer: Establishing a Standard for Patient Safety and Monitoring

2013 ◽  
Vol 98 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Aubrey A. Carhill ◽  
Maria E. Cabanillas ◽  
Camilo Jimenez ◽  
Steven G. Waguespack ◽  
Mouhammed A. Habra ◽  
...  
Keyword(s):  
Patient Safety ◽  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors

Effect of the Tyrosine Kinase Inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) On Blood Glucose Levels in Diabetic and Non-Diabetic Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4265-4265
Author(s):  
Nicole M. Agostino ◽  
Vernon M Chinchilli ◽  
Anita Koszyk-Szewczyk ◽  
Rebecca Gingrich ◽  
Jeff Sivik ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels

Abstract Abstract 4265 Background Tyrosine kinase is a key enzyme utilized in many intracellular messaging pathways. Understanding of the role of particular tyrosine kinases in various malignancies has allowed for the design of compounds, the tyrosine kinase inhibitors (TKIs), which can specifically target these enzymes and hence, interfere with downstream signaling. TKIs have proven to be very successful in the treatment of a wide variety of malignant diseases including chronic myeloid leukemia, Philadelphia chromosome positive acute lymphoblastic leukemia, renal cell carcinoma and gastrointenstinal stromal tumors. Given the widespread nature of tyrosine kinase as a target and the promiscuous nature of the various inhibitors, it would not be surprising that these drugs would have effects beyond the expected result of targeting merely the tyrosine kinase of interest. Scattered reports have suggested that these agents appear to affect blood glucose levels. Results We studied the blood glucose levels retrospectively in diabetic (19) and non-diabetic (82) patients treated with dasatinib (8), imatinib (39), sorafenib (23) and sunitinib (30). All 4 drugs resulted in statistically significant decreased blood glucose levels in both diabetic and non-diabetic patients that resolved with cessation of treatment. Mean decreases blood glucose values for both non-diabetic and diabetic patients for dasatinib were – 53 mg/dl, imatinib – 9 mg/dl, sorafenib – 12 mg/dl and sunitinib -14 mg/dl. While diabetic and non-diabetic patients had the same decreases in blood glucose, on average, blood glucose values overall were 40 mg/dl lower in non-diabetic patients than in diabetic patients on dasatanib and imatinib. Non-diabetics had an overall mean blood glucose value of 24 mg/dl lower than diabetic patients on sorafenib, and 15 mg/dl lower than diabetic patients on sunitinib. Diabetic patients required some modifications of their medications including cessation of insulin or other hypoglycemic agents. One diabetic patient developed symptomatic hypoglycemia on sunitinib. Discussion The mechanism for the hypoglycemic effect of these drugs is unclear, but of the 4 agents tested, c-kit is a common target. C-kit has been shown to play a role in pancreatic β-cell survival in mouse models, so it is unclear why an inhibitor of the c-kit tyrosine kinase would improve blood glucose levels. It is important for clinicians to keep the potentially hypoglycemic effects of these agents in mind in their patients since symptomatic hypoglycemia can occur and modification of hypoglycemic agents may be required. These results also suggest that inhibition of a tyrosine kinase, be it c-kit or some other undefined target, may improve diabetes mellitus and deserves further study as a potentially therapeutic option. Disclosures: No relevant conflicts of interest to declare.

P5717Risk of QTC interval prolongation among cancer patients treated with tyrosine kinase inhibitors

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Abu Rmilah ◽  
G Lin ◽  
J Hermann
Keyword(s):  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Complication Rates ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qtc Prolongation ◽  
Qtc Interval Prolongation ◽  
Life Threatening

Abstract Objective 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, the 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. Table 1 demonstrates the findings for each TKI. Findings for TKIs in all patients Total Prolonged QTc QTc ≥500 QTc progression ≥60 VT SCD TdP Imatinib 165 54 13 10 2 Nilotinib 75 33 8 19 Dasatinib 115 58 10 16 2 1 Sunitinib 134 31 1 2 1 1 Pazopanib 165 36 5 6 2 1 Others 248 77 16 18 2 1 1 Conclusion 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. Acknowledgement/Funding None

scholarly journals Hypertensive toxicity of thyrosine kinase inhibitors; Friend or Foe?

2021 ◽  
Vol 5 (1) ◽  
pp. 001-002
Author(s):  
Kaya Ergün Barış ◽  
Şener Yusuf Ziya
Keyword(s):  
Tyrosine Kinase ◽  
Cancer Treatment ◽  
Clinical Outcomes ◽  
Tyrosine Kinase Inhibitors ◽  
Treatment Efficacy ◽  
Kinase Inhibitors ◽  
Oncology Practice

Tyrosine kinase inhibitors (TKIs) are widely used in Oncology practice. Hypertension may develop during cancer treatment and TKIs are well known drugs that are associated with drug related hypertensive toxicity. TKI related hypertensive toxicity is not always the indicator of worse clinical outcomes and it may be the sign of treatment efficacy.

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