{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:42:57Z","timestamp":1763116977088,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.<\/jats:p>","DOI":"10.3390\/dj10120232","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T02:17:57Z","timestamp":1670465877000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib\u2014Report of Three Cases"],"prefix":"10.3390","volume":"10","author":[{"given":"Erofili","family":"Papadopoulou","sequence":"first","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanouil","family":"Vardas","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Styliani","family":"Tziveleka","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Georgaki","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-4911","authenticated-orcid":false,"given":"Maria","family":"Kouri","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Katoumas","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-1837","authenticated-orcid":false,"given":"Evangelia","family":"Piperi","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Nikitakis","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, NKUA, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s00520-017-3629-4","article-title":"Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors","volume":"25","author":"Vigarios","year":"2017","journal-title":"Support. Care Cancer"},{"key":"ref_2","first-page":"26","article-title":"Oral adverse events associated with targeted cancer therapies","volume":"66","author":"Chmieliauskaite","year":"2018","journal-title":"Gen. Dent."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s40496-015-0069-4","article-title":"Oral Mucositis Induced by Anticancer Therapies","volume":"2","author":"Zecha","year":"2015","journal-title":"Curr. Oral Health Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.oraloncology.2011.03.028","article-title":"Oral complications of targeted cancer therapies: A narrative literature review","volume":"47","author":"Watters","year":"2011","journal-title":"Oral Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biopha.2018.12.022","article-title":"Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases","volume":"110","author":"Fallah","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Comandone, A., Vana, F., Comandone, T., and Tucci, M. (2021). Antiangiogenic Therapy in Clear Cell Renal Carcinoma (CCRC): Pharmacological Basis and Clinical Results. Cancers, 13.","DOI":"10.3390\/cancers13235896"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.bjoms.2021.03.006","article-title":"Systematic review of medication related osteonecrosis of the jaw (MRONJ) in patients undergoing only antiangiogenic drug therapy: Surgery or conservative therapy?","volume":"60","author":"Sacco","year":"2022","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.31744\/einstein_journal\/2019RW4628","article-title":"Risk profile for antiangiogenic agent-related osteonecrosis of the jaws","volume":"17","author":"Caminha","year":"2019","journal-title":"Einstein"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.omsc.2017.03.001","article-title":"Osteonecrosis of jaw after angiogenic agent administration in a renal cell carcinoma patient","volume":"3","author":"Jung","year":"2017","journal-title":"Oral Maxillofac. Surg. Cases"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.2174\/0929867324666170511113811","article-title":"Osteonecrosis of the jaw and angiogenesis inhibitors: A revival of a rare but serious side effect","volume":"24","author":"Antonuzzo","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/8071579","article-title":"Osteonecrosis of the Jaw Associated with Antiangiogenics in Antiresorptive-Na\u00efve Patient: A Comprehensive Review of the Literature","volume":"23","author":"Pimolbutr","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40257-018-0384-3","article-title":"Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails","volume":"19","author":"Lacouture","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.joms.2014.04.031","article-title":"American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update","volume":"72","author":"Ruggiero","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1111\/odi.13160","article-title":"Workshop of European task force on medication-related osteonecrosis of the jaw-Current challenges","volume":"25","author":"Schiodt","year":"2019","journal-title":"Oral Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.oooo.2017.08.003","article-title":"Axitinib-related osteonecrosis of the jaw","volume":"124","author":"Patel","year":"2017","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/jjco\/hyy053","article-title":"Drug review: Pazopanib","volume":"48","author":"Miyamoto","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1634\/theoncologist.2011-S2-14","article-title":"Targeted therapies for the treatment of metastatic renal cell carcinoma: Clinical evidence","volume":"16","author":"Hutson","year":"2011","journal-title":"Oncologist"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00520-018-4501-x","article-title":"Osteonecrosis of the jaw related to non-antiresorptive medications: A systematic review","volume":"27","author":"Kouri","year":"2019","journal-title":"Support. Care Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.critrevonc.2017.10.014","article-title":"Examining the bleeding incidences associated with targeted therapies used in metastatic renal cell carcinoma","volume":"120","author":"Crist","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.tripleo.2011.08.024","article-title":"Gingival bleeding and jaw bone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: Report of 2 cases with clinical implications","volume":"113","author":"Migkou","year":"2012","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_22","first-page":"54","article-title":"Gingival bleeding in a patient with cervical cancer receiving bevacizumab. Report of a case","volume":"1","author":"Papadopoulou","year":"2012","journal-title":"MOJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1634\/theoncologist.2011-0111","article-title":"Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: A structured literature review","volume":"17","author":"Epstein","year":"2012","journal-title":"Oncologist"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.oraloncology.2011.01.002","article-title":"Efficacy and safety of medical ozone (O3) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I\u2013II study","volume":"47","author":"Ripamonti","year":"2011","journal-title":"Oral Oncol."},{"key":"ref_25","first-page":"895","article-title":"Chamomile: A herbal medicine of the past with bright future","volume":"3","author":"Srivastava","year":"2010","journal-title":"Mol. Med. Rep."},{"key":"ref_26","first-page":"935","article-title":"Chamomile: An anti-inflammatory agent inhibits inducible nitric oxide synthase expression by blocking RelA\/p65 activity","volume":"26","author":"Bhaskaran","year":"2010","journal-title":"Int. J. Mol. 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