- Email: [email protected]
Oral tyrosine kinase inhibitors in OMFS: a review
YBJOM-5862;
No. of Pages 4
ARTICLE IN PRESS Available online at www.sciencedirect.com
ScienceDirect British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Review
Oral tyrosine kinase inhibitors in OMFS: a review P. Shah, F. Dylgjeri, B. Srinivasan ∗ , P.A. Brennan Department of OMFS, Queen Alexandra Hospital, Cosham, UK
Abstract It is increasingly common in OMFS to treat patients who are taking therapeutic doses of anticoagulant or antiplatelet drugs, or both. These patients have a high risk of postoperative bleeding ranging from minor oozing that can be managed using local measures, to a major haemorrhage necessitating transfusion. The risk of bleeding associated with tyrosine kinase inhibitors (TKI) taken orally is not well-known in the specialty. We report a case series of two patients treated with them and discuss this group of drugs. Crown Copyright © 2020 Published by Elsevier Ltd on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved. Keywords: review; tyrosine kinase inhibitors; oral and maxillofacial surgery; bleeding
Introduction Tyrosine kinase inhibitors (TKI) taken orally, which are relatively little known in OMFS, are used in the treatment of malignancies such as chronic myelogenous leukaemia, renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumour.1 Examples are sunitinib (Fig. 1) for the treatment of renal cell carcinoma and gastrointestinal stromal tumour; ibrutinib (Fig. 2) for chronic lymphocytic leukaemia; sorafenib for hepatocellular carcinoma; and regorafenib for gastrointestinal stromal tumour.1,2 Kinases form a group of enzymes that have a role in phosphorylation.1 Phosphorylation involves the transference of phosphate groups of donor molecules such as adenosine5 -triphosphate (ATP) to substrates, where they are catalysed by kinases. TKI act on tyrosine sites, as they block the ATPbinding site on receptors. They are largely metabolised and eliminated through the hepatic system,1 but can cause thrombocytopaenia and anaemia, which can be problematic during surgery. To our knowledge, no published reports on their use
∗
Corresponding author. Tel.: +44 7910187543. E-mail addresses: [email protected] (P. Shah), [email protected] (F. Dylgjeri), [email protected] (B. Srinivasan), [email protected] (P.A. Brennan).
have been relevant to patients treated in OMFS, and colleagues do not seem to be aware of the problems they can cause. We describe the cases of two patients who were taking these drugs and discuss their management. Case 1 A 75-year-old man presented with multiple facial basal cell carcinomas. He had low-grade lymphoproliferative disorder and had recently started taking ibrutinib. After resection and repair of all the lesions with local flaps and skin grafts he had slow ooze from all the surgical sites (despite a platelet count of 100), which stopped at day five with local measures and pressure dressing. Three weeks after the initial resection the wounds had healed well. Case 2 A 77-year-old man with a new diagnosis of advanced squamous cell carcinoma (SCC) of the left mandibular alveolus had recently started sunitinib to downstage a renal cancer before resection. After discussion at the multidisciplinary team meeting, operation was recommended with curative intent, but as there was concern that stopping the drug for a few weeks to facilitate surgery could result in the cancer progressing, he was managed with radiotherapy.
https://doi.org/10.1016/j.bjoms.2019.11.022 0266-4356/Crown Copyright © 2020 Published by Elsevier Ltd on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862;
ARTICLE IN PRESS
No. of Pages 4
2
P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Fig. 1. Chemical structure of sunitinib. Fig. 2. Chemical structure for ibrutinib.
Discussion Several medications are associated with an increased risk of bleeding and they warrant a certain degree of caution before any operation. These include aspirin, clopidogrel, warfarin, low molecular weight heparin (LMWH), unfractionated hep-
arin, ticagrelor, and novel oral anticoagulants (NOAC) such as apixaban, rivaroxaban, and dabigatran. Oral TKI are not currently in the group of medications known in OMFS to cause serious postoperative bleeding diathesis. Their indications and mechanism of action are presented in Table 1.3–10
Table 1 Mechanism of action of the commonly-used drugs associated with an increased risk of bleeding. Drug Aspirin
Clopidogrel Warfarin
Low molecular weight heparin (LMWH)
Unfractioned heparin
Ticagrelor Apixaban
Rivaroxaban
Dabigatran
Indications
Mechanism of action
Prophylaxis of primary myocardial infarction (MI) and secondary prophylaxis after MI After percutaneous coronary intervention (PCI)3 Prophylaxis of primary MI and secondary prophylaxis after MI3 Atrial fibrillation Cardioversion DVT/PE4 Treatment and prophylaxis of VTE/PE in patients for whom warfarin or direct oral anticoagulant is contraindicated including patients who are intravenous drug users. Prophylaxis of VTE postoperatively (hips, knees, general surgical)5 Prophylaxis and treatment of VTE/PE Prophylaxis of mural thrombosis after MI Treatment of angina/MI Perioperatively in chronic AF for elective procedures7 Prophylaxis of atherothrombotic events in acute coronary syndrome or in patients with a history of MI8 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults9 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults9 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults8
Cyclo-oxygenase inhibitor. It decreases arachidonic acid metabolite production, which activates platelets such as thromboxanes3 Second-generation thienopyridine (irreversible platelet P2Y12 receptor blocker)3 Vitamin K antagonist4
Activates antithrombin III. Antithrombin III binds to and inhibits factor Xa6
Inactivates thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism7 Inhibits platelet function as it reversibly blocks P2Y12 receptor3 Factor Xa inhibitor4
Factor Xa inhibitor10
Direct thrombin inhibitor4
DVT: deep vein thrombosis; PE: pulmonary embolism; VTE: venous thromboembolism; AF: atrial fibrillation.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862;
No. of Pages 4
ARTICLE IN PRESS P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Anticoagulant and antiplatelet drugs are used prophylactically or therapeutically, or both, in the treatment of cardiovascular, cerebrovascular, and peripheral vascular diseases, as well as other conditions, and their use affects the risk of perioperative haemorrhage. TKI have many reported side effects including alopecia, anaemia, diarrhoea, depression, dysphagia, gastrointestinal disorders, headache, hypertension, haemorrhage, myocardial infarction, renal failure, and thrombocytopenia.11 Sunitinib and sorafenib are TKI taken orally, and they work by blocking receptors such as VEGF-2 (VEGFR-2), VEGF-3 (VEGFR-3), and PDGF- (PDGFR-) to prevent an intracellular cascade that leads to tumorigenesis and metastasis.12,13 Sunitinib, which is used in the treatment of metastatic renal cell carcinoma,12 also prevents the proliferation of endothelial cells and vascularisation through its action on PDGF, and so inhibits the proliferation of pericytes and fibroblasts, which are necessary for the maintenance of endothelial cells. In clinical trials both sorafenib and sunitinib have been associated with bleeding, and side effects include gastric ulceration, stomatitis, and mucositis. Although uncommon, severe life-threatening gastric haemorrhage for which emergency endoscopic haemostasis was necessary, has also been reported.13 Sunitinib has been linked with serious oral side effects such as altered taste, sensitivity of the mouth, and stomatitis, which necessitate gentle methods of oral hygiene such as brushing with toothpaste and mouth rinses that do not contain alcohol. An antimicrobial mouthwash such as chlorhexidine gluconate 0.12% should be considered together with analgesic mouthwashes such as 2% lidocaine hydrochloride.14 Ibrutinib is used in the treatment of chronic lymphocytic leukaemia. It blocks Bruton’s tyrosine kinase, which affects enzymatic activity that inhibits the B-cell receptor (BCR) pathway, prevents cell growth and proliferation, and diminishes malignant B cells.2,15 It has been reported to cause low-grade ecchymoses15 and petechiae16 in 50% of patients, and major haemorrhage in 1%.17 This bleeding was largely perioperative, but spontaneous haemorrhage has also been noted and attributed to an impairment in the aggregation of collagen-induced platelets, and adhesion of platelets under high shear conditions.15 The risk of haemorrhage is high during any operation on the head and neck, and prolonged bleeding at the surgical site in a confined space can compromise the airway, slow postoperative healing, and increase the risk of infection. In conclusion, as TKI taken orally are increasingly being used to treat metastatic cancers in patients who require operations on the head and neck, it is imperative that surgeons are aware of the risk of bleeding and how best to manage it. We would like to emphasise the importance of taking a thorough history to ascertain all the medications that the patient is taking and to assess the risk of bleeding appropriately. Prompt liaison with the oncology team to weigh up the risks and the benefits of discontinuing these drugs should be considered.
3
Ethics statement/confirmation of patients’ permission Not required.
Conflict of interest We have no conflicts of interest.
References 1. Jeong W, Doroshow JH, Kummar S. United States Food and Drug Administration approved oral kinase inhibitors for the treatment of malignancies. Curr Probl Cancer 2013;37:110–44. 2. Parmar S, Patel K, Pinilla-Ibarz J. Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. P T 2014;39:483–519. 3. Johnstone N, Jadhav S, Subramanian G. Guideline for patients on antiplatelet agents undergoing elective, non-cardiac surgical intervention; 2018. Available from URL: https://www.nuh.nhs.uk/ download.cfm?doc=docm93jijm4n3981.pdf&ver=6881 (last accessed 16 November 2019). 4. Foster A, Dasgupta Dr. Oral anticoagulants (VKA and NOAC): guidelines for prescribing, monitoring and management. Wirral Clinical Commissioning Group; 2015. Available from URL: http://mm.wirral. nhs.uk/document uploads/guidelines/AnticoagulantOralGuidelines forprescribingmonitoringandmanagement.pdf (last accessed 16 November 2019). 5. Lancashire and South Cumbria Medicines Management Group. Low molecular weight heparins (LMWHs): summary prescribing guide. Available from URL: https://www.lancsmmg.nhs.uk/download/ guidelines/Low-Molecular-Weigh-Heparins-Summary-Prescribingguide-Version-1.4.pdf (last accessed 16 November 2019). 6. Solari F, Varacallo M. Low molecular weight heparin (LMWH) (updated February 2019). StatPearls Publishing; 2019. Available from URL: https://www.ncbi.nlm.nih.gov/books/NBK525957/ (last accessed 19 November 2019). 7. Hirsh J, Anand SS, Halperin JL, et al. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 2001;21:1094–6. 8. National Institute for Health and Care Excellence. Ticagrelor. British National Formulary (BNF) May; 2019. Available from URL: https://bnf.nice.org.uk/drug/ticagrelor.html#indicationsAndDoses (last accessed 19 November 2019). 9. Barts Health NHS Trust. Guideline on selecting appropriate non-vitamin K antagonist oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs); 2016. Available from URL: https://www.sps.nhs. uk/wp-content/uploads/2018/02/Guideline-selecting-NOACs-finalSept-2016-8s1.1.d.pdf (last accessed 19 November 2019). 10. National Institute for Health and Care Excellence. Sorafenib. British National Formulary (BNF) May; 2019. Available from URL: https://bnf.nice.org.uk/drug/sorafenib.html (last accessed 16 November 2019). 11. Hansen CR, Grimm D, Bauer J, et al. Effects and side effects of using sorafenib and sunitinib in the treatment of metastatic renal cell carcinoma. Int J Mol Sci 2017;18:461. 12. Fujihara S, Mori H, Kobara H, et al. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: a report of four cases. Oncol Lett 2015;10:2895–8. 13. Schwandt A, Wood LS, Rini B, et al. Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Onco Targets Ther 2009;2:51–61. 14. Brown JR. How I treat CLL patients with ibrutinib. Blood 2018;131:379–86.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862; 4
No. of Pages 4
ARTICLE IN PRESS P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
15. Jaglowski SM, Jones JA, Flynn JM, et al. A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI32765 and of atumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. J Clin Oncol 2012;30:6508. Available from URL: https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15 suppl.6508 (last accessed 25 November 2019).
16. Jones JA, Hillmen P, Coutre S, et al. Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib. Br J Haematol 2017;178:286–91. 17. O’Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol 2016;17:1409–18.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
No. of Pages 4
ARTICLE IN PRESS Available online at www.sciencedirect.com
ScienceDirect British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Review
Oral tyrosine kinase inhibitors in OMFS: a review P. Shah, F. Dylgjeri, B. Srinivasan ∗ , P.A. Brennan Department of OMFS, Queen Alexandra Hospital, Cosham, UK
Abstract It is increasingly common in OMFS to treat patients who are taking therapeutic doses of anticoagulant or antiplatelet drugs, or both. These patients have a high risk of postoperative bleeding ranging from minor oozing that can be managed using local measures, to a major haemorrhage necessitating transfusion. The risk of bleeding associated with tyrosine kinase inhibitors (TKI) taken orally is not well-known in the specialty. We report a case series of two patients treated with them and discuss this group of drugs. Crown Copyright © 2020 Published by Elsevier Ltd on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved. Keywords: review; tyrosine kinase inhibitors; oral and maxillofacial surgery; bleeding
Introduction Tyrosine kinase inhibitors (TKI) taken orally, which are relatively little known in OMFS, are used in the treatment of malignancies such as chronic myelogenous leukaemia, renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumour.1 Examples are sunitinib (Fig. 1) for the treatment of renal cell carcinoma and gastrointestinal stromal tumour; ibrutinib (Fig. 2) for chronic lymphocytic leukaemia; sorafenib for hepatocellular carcinoma; and regorafenib for gastrointestinal stromal tumour.1,2 Kinases form a group of enzymes that have a role in phosphorylation.1 Phosphorylation involves the transference of phosphate groups of donor molecules such as adenosine5 -triphosphate (ATP) to substrates, where they are catalysed by kinases. TKI act on tyrosine sites, as they block the ATPbinding site on receptors. They are largely metabolised and eliminated through the hepatic system,1 but can cause thrombocytopaenia and anaemia, which can be problematic during surgery. To our knowledge, no published reports on their use
∗
Corresponding author. Tel.: +44 7910187543. E-mail addresses: [email protected] (P. Shah), [email protected] (F. Dylgjeri), [email protected] (B. Srinivasan), [email protected] (P.A. Brennan).
have been relevant to patients treated in OMFS, and colleagues do not seem to be aware of the problems they can cause. We describe the cases of two patients who were taking these drugs and discuss their management. Case 1 A 75-year-old man presented with multiple facial basal cell carcinomas. He had low-grade lymphoproliferative disorder and had recently started taking ibrutinib. After resection and repair of all the lesions with local flaps and skin grafts he had slow ooze from all the surgical sites (despite a platelet count of 100), which stopped at day five with local measures and pressure dressing. Three weeks after the initial resection the wounds had healed well. Case 2 A 77-year-old man with a new diagnosis of advanced squamous cell carcinoma (SCC) of the left mandibular alveolus had recently started sunitinib to downstage a renal cancer before resection. After discussion at the multidisciplinary team meeting, operation was recommended with curative intent, but as there was concern that stopping the drug for a few weeks to facilitate surgery could result in the cancer progressing, he was managed with radiotherapy.
https://doi.org/10.1016/j.bjoms.2019.11.022 0266-4356/Crown Copyright © 2020 Published by Elsevier Ltd on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862;
ARTICLE IN PRESS
No. of Pages 4
2
P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Fig. 1. Chemical structure of sunitinib. Fig. 2. Chemical structure for ibrutinib.
Discussion Several medications are associated with an increased risk of bleeding and they warrant a certain degree of caution before any operation. These include aspirin, clopidogrel, warfarin, low molecular weight heparin (LMWH), unfractionated hep-
arin, ticagrelor, and novel oral anticoagulants (NOAC) such as apixaban, rivaroxaban, and dabigatran. Oral TKI are not currently in the group of medications known in OMFS to cause serious postoperative bleeding diathesis. Their indications and mechanism of action are presented in Table 1.3–10
Table 1 Mechanism of action of the commonly-used drugs associated with an increased risk of bleeding. Drug Aspirin
Clopidogrel Warfarin
Low molecular weight heparin (LMWH)
Unfractioned heparin
Ticagrelor Apixaban
Rivaroxaban
Dabigatran
Indications
Mechanism of action
Prophylaxis of primary myocardial infarction (MI) and secondary prophylaxis after MI After percutaneous coronary intervention (PCI)3 Prophylaxis of primary MI and secondary prophylaxis after MI3 Atrial fibrillation Cardioversion DVT/PE4 Treatment and prophylaxis of VTE/PE in patients for whom warfarin or direct oral anticoagulant is contraindicated including patients who are intravenous drug users. Prophylaxis of VTE postoperatively (hips, knees, general surgical)5 Prophylaxis and treatment of VTE/PE Prophylaxis of mural thrombosis after MI Treatment of angina/MI Perioperatively in chronic AF for elective procedures7 Prophylaxis of atherothrombotic events in acute coronary syndrome or in patients with a history of MI8 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults9 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults9 Prophylaxis of stroke and systemic embolism in non-valvular AF Treatment and secondary prevention of DVT/PE Prophylaxis of VTE after total hip (35 days) or knee (14 days) replacement in adults8
Cyclo-oxygenase inhibitor. It decreases arachidonic acid metabolite production, which activates platelets such as thromboxanes3 Second-generation thienopyridine (irreversible platelet P2Y12 receptor blocker)3 Vitamin K antagonist4
Activates antithrombin III. Antithrombin III binds to and inhibits factor Xa6
Inactivates thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism7 Inhibits platelet function as it reversibly blocks P2Y12 receptor3 Factor Xa inhibitor4
Factor Xa inhibitor10
Direct thrombin inhibitor4
DVT: deep vein thrombosis; PE: pulmonary embolism; VTE: venous thromboembolism; AF: atrial fibrillation.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862;
No. of Pages 4
ARTICLE IN PRESS P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
Anticoagulant and antiplatelet drugs are used prophylactically or therapeutically, or both, in the treatment of cardiovascular, cerebrovascular, and peripheral vascular diseases, as well as other conditions, and their use affects the risk of perioperative haemorrhage. TKI have many reported side effects including alopecia, anaemia, diarrhoea, depression, dysphagia, gastrointestinal disorders, headache, hypertension, haemorrhage, myocardial infarction, renal failure, and thrombocytopenia.11 Sunitinib and sorafenib are TKI taken orally, and they work by blocking receptors such as VEGF-2 (VEGFR-2), VEGF-3 (VEGFR-3), and PDGF- (PDGFR-) to prevent an intracellular cascade that leads to tumorigenesis and metastasis.12,13 Sunitinib, which is used in the treatment of metastatic renal cell carcinoma,12 also prevents the proliferation of endothelial cells and vascularisation through its action on PDGF, and so inhibits the proliferation of pericytes and fibroblasts, which are necessary for the maintenance of endothelial cells. In clinical trials both sorafenib and sunitinib have been associated with bleeding, and side effects include gastric ulceration, stomatitis, and mucositis. Although uncommon, severe life-threatening gastric haemorrhage for which emergency endoscopic haemostasis was necessary, has also been reported.13 Sunitinib has been linked with serious oral side effects such as altered taste, sensitivity of the mouth, and stomatitis, which necessitate gentle methods of oral hygiene such as brushing with toothpaste and mouth rinses that do not contain alcohol. An antimicrobial mouthwash such as chlorhexidine gluconate 0.12% should be considered together with analgesic mouthwashes such as 2% lidocaine hydrochloride.14 Ibrutinib is used in the treatment of chronic lymphocytic leukaemia. It blocks Bruton’s tyrosine kinase, which affects enzymatic activity that inhibits the B-cell receptor (BCR) pathway, prevents cell growth and proliferation, and diminishes malignant B cells.2,15 It has been reported to cause low-grade ecchymoses15 and petechiae16 in 50% of patients, and major haemorrhage in 1%.17 This bleeding was largely perioperative, but spontaneous haemorrhage has also been noted and attributed to an impairment in the aggregation of collagen-induced platelets, and adhesion of platelets under high shear conditions.15 The risk of haemorrhage is high during any operation on the head and neck, and prolonged bleeding at the surgical site in a confined space can compromise the airway, slow postoperative healing, and increase the risk of infection. In conclusion, as TKI taken orally are increasingly being used to treat metastatic cancers in patients who require operations on the head and neck, it is imperative that surgeons are aware of the risk of bleeding and how best to manage it. We would like to emphasise the importance of taking a thorough history to ascertain all the medications that the patient is taking and to assess the risk of bleeding appropriately. Prompt liaison with the oncology team to weigh up the risks and the benefits of discontinuing these drugs should be considered.
3
Ethics statement/confirmation of patients’ permission Not required.
Conflict of interest We have no conflicts of interest.
References 1. Jeong W, Doroshow JH, Kummar S. United States Food and Drug Administration approved oral kinase inhibitors for the treatment of malignancies. Curr Probl Cancer 2013;37:110–44. 2. Parmar S, Patel K, Pinilla-Ibarz J. Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. P T 2014;39:483–519. 3. Johnstone N, Jadhav S, Subramanian G. Guideline for patients on antiplatelet agents undergoing elective, non-cardiac surgical intervention; 2018. Available from URL: https://www.nuh.nhs.uk/ download.cfm?doc=docm93jijm4n3981.pdf&ver=6881 (last accessed 16 November 2019). 4. Foster A, Dasgupta Dr. Oral anticoagulants (VKA and NOAC): guidelines for prescribing, monitoring and management. Wirral Clinical Commissioning Group; 2015. Available from URL: http://mm.wirral. nhs.uk/document uploads/guidelines/AnticoagulantOralGuidelines forprescribingmonitoringandmanagement.pdf (last accessed 16 November 2019). 5. Lancashire and South Cumbria Medicines Management Group. Low molecular weight heparins (LMWHs): summary prescribing guide. Available from URL: https://www.lancsmmg.nhs.uk/download/ guidelines/Low-Molecular-Weigh-Heparins-Summary-Prescribingguide-Version-1.4.pdf (last accessed 16 November 2019). 6. Solari F, Varacallo M. Low molecular weight heparin (LMWH) (updated February 2019). StatPearls Publishing; 2019. Available from URL: https://www.ncbi.nlm.nih.gov/books/NBK525957/ (last accessed 19 November 2019). 7. Hirsh J, Anand SS, Halperin JL, et al. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 2001;21:1094–6. 8. National Institute for Health and Care Excellence. Ticagrelor. British National Formulary (BNF) May; 2019. Available from URL: https://bnf.nice.org.uk/drug/ticagrelor.html#indicationsAndDoses (last accessed 19 November 2019). 9. Barts Health NHS Trust. Guideline on selecting appropriate non-vitamin K antagonist oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs); 2016. Available from URL: https://www.sps.nhs. uk/wp-content/uploads/2018/02/Guideline-selecting-NOACs-finalSept-2016-8s1.1.d.pdf (last accessed 19 November 2019). 10. National Institute for Health and Care Excellence. Sorafenib. British National Formulary (BNF) May; 2019. Available from URL: https://bnf.nice.org.uk/drug/sorafenib.html (last accessed 16 November 2019). 11. Hansen CR, Grimm D, Bauer J, et al. Effects and side effects of using sorafenib and sunitinib in the treatment of metastatic renal cell carcinoma. Int J Mol Sci 2017;18:461. 12. Fujihara S, Mori H, Kobara H, et al. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: a report of four cases. Oncol Lett 2015;10:2895–8. 13. Schwandt A, Wood LS, Rini B, et al. Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Onco Targets Ther 2009;2:51–61. 14. Brown JR. How I treat CLL patients with ibrutinib. Blood 2018;131:379–86.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022
YBJOM-5862; 4
No. of Pages 4
ARTICLE IN PRESS P. Shah et al. / British Journal of Oral and Maxillofacial Surgery xxx (2020) xxx–xxx
15. Jaglowski SM, Jones JA, Flynn JM, et al. A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI32765 and of atumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. J Clin Oncol 2012;30:6508. Available from URL: https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15 suppl.6508 (last accessed 25 November 2019).
16. Jones JA, Hillmen P, Coutre S, et al. Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib. Br J Haematol 2017;178:286–91. 17. O’Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol 2016;17:1409–18.
Please cite this article in press as: Shah P, et al. Oral tyrosine kinase inhibitors in OMFS: a review. Br J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.bjoms.2019.11.022