Tyrosine kinase inhibitors in cancer treatment (Part II)

Purpose Pneumatosis intestinalis is a radiologic diagnosis that manifests in a variety of clinical settings. We report 4 cases of pneumatosis intestinalis in patients undergoing cancer treatments that included cytotoxic agents and/or tyrosine kinase inhibitors. These reports aim to provide insight into the clinical interpretation and pathogenesis of pneumatosis intestinalis in the setting of cancer treatments and demonstrate a potential association with tyrosine kinase inhibitors. Methods Radiologists responsible for the interpretation of adult imaging at our tertiary care centre were surveyed to identify cases of pneumatosis intestinalis arising in the midst of cancer treatment. The case histories were reviewed by physicians with expertise in cancer treatment. Results Four cases of chemotherapy-related pneumatosis intestinalis were identified. The diagnosis was made in 1 patient during investigations undertaken for non–life-threatening abdominal symptoms and incidentally in 2 patients by abdominal imaging used to measure chemotherapy response. A fourth patient presented in a life-threatening manner, and abdominal imaging was symptom guided. Interestingly, 3 of the 4 patients were receiving treatments that included a tyrosine kinase inhibitor, and this agent was the only identifiable potential etiology in 1 patient. Conclusions The significance of pneumatosis intestinalis arising during cancer treatments is difficult to interpret because of the complex nature of the diseases and the treatments that often include combinations of cytotoxic agents and/or novel therapies. These reports demonstrate the importance of classifying this radiologic finding according clinical severity rather than etiology and underscore the need for continued observation for unexplained adverse effects when using novel therapies.

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Multiparameter Evaluation of the Platelet-Inhibitory Effects of Tyrosine Kinase Inhibitors Used for Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms222011199 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11199

Author(s):

Bibian M. E. Tullemans ◽

Alicia Veninga ◽

Delia I. Fernandez ◽

Maureen J. B. Aarts ◽

Johannes A. Eble ◽

...

Keyword(s):

Tyrosine Kinase ◽

Cancer Treatment ◽

Intracellular Calcium ◽

Tyrosine Kinase Inhibitors ◽

Whole Blood ◽

Kinase Inhibitors ◽

Thrombus Formation ◽

Antiplatelet Drugs ◽

Glycoprotein Vi ◽

Induced Aggregation

Current antiplatelet drugs for the treatment of arterial thrombosis often coincide with increased bleeding risk. Several tyrosine kinase inhibitors (TKIs) for cancer treatment inhibit platelet function, with minor reported bleeding symptoms. The aim of this study was to compare the antiplatelet properties of eight TKIs to explore their possible repurposing as antiplatelet drugs. Samples of whole blood, platelet-rich plasma (PRP), or isolated platelets from healthy donors were treated with TKI or the vehicle. Measurements of platelet aggregation, activation, intracellular calcium mobilization, and whole-blood thrombus formation under flow were performed. Dasatinib and sunitinib dose-dependently reduced collagen-induced aggregation in PRP and washed platelets; pazopanib, cabozantinib, and vatalanib inhibited this response in washed platelets only; and fostamatinib, axitinib, and lapatinib showed no/limited effects. Fostamatinib reduced thrombus formation by approximately 50% on collagen and other substrates. Pazopanib, sunitinib, dasatinib, axitinib, and vatalanib mildly reduced thrombus formation on collagen by 10–50%. Intracellular calcium responses in isolated platelets were inhibited by dasatinib (>90%), fostamatinib (57%), sunitinib (77%), and pazopanib (82%). Upon glycoprotein-VI receptor stimulation, fostamatinib, cabozantinib, and vatalanib decreased highly activated platelet populations by approximately 15%, while increasing resting populations by 39%. In conclusion, the TKIs with the highest affinities for platelet-expressed molecular targets most strongly inhibited platelet functions. Dasatinib, fostamatinib, sunitinib, and pazopanib interfered in early collagen receptor-induced molecular-signaling compared with cabozantinib and vatalanib. Fostamatinib, sunitinib, pazopanib, and vatalanib may be promising for future evaluation as antiplatelet drugs.

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