Sunitinib is an oral, multi-targeted tyrosine kinase inhibitor that inhibits the vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor (PDGFR), the stem cell factor receptor (SCF or c-Kit), and the colony-stimulating factor-1 receptor.1 It was approved for the treatment of renal and gastrointestinal stromal tumors2 and also recently showed anti-tumor activity in patients with metastatic breast cancer.1 This case is the first to describe the oral clinical aspects of sunitinib-suspected oral mucositis toxicity in a breast cancer patient. Although the frequency of grade 3/4 toxicities occurring with Sunitinib is relatively low (< 10%), mostly reported in renal cell cancer rather than metastatic breast cancer studies, the oral adverse event, always described as stomatitis or mucositis, occurred with varying frequency nonetheless (10-30%).3 This case is unique because for the first time it describes the oral clinical aspects of sunitinib-induced stomatitis, characterized by bullous and erosive lesions with widespread lichenoid and necrotizing areas which appeared 12 hours after the second day of the third cycle. She discontinued sunitinib and received prednisone (25 mg PO qd) for three days, followed by topical corticosteroids such as mouthwash bid for seven days. The patient was counseled to modify her diet regimen, eat soft foods, drink non-alcoholic liquids with a straw, and to maintain meticulous oral hygiene by using a toothbrush with soft bristles and a diluted solution of chlorexidine 0.12% as a mouthwash in case of bleeding gums.3 Ten days later she was in complete clinical remission. The patient was not re-challenge, because she refused to take the medication again. Although the first target of sunitinib is the capillary endothelium which blocks VEGFR 1/2/3, PDGFR, c-Kit and Flt-3 (FMS-like tyrosine kinase 3), the presence of these receptors has also been detected in other tissue, e.g., c-Kit in the acini and ducts of salivary glands,4 in human keratinocytes,5 and VEGFR-1 in the epidermal layer of unwounded skin. It is likely that the initial damage induced by suninib in the oral cavity may affect not only vascular tissue, but even salivary glands and keratinocytes. Once the damage is established, these lesions might self-maintain, due to an impairment of wound healing mechanisms. In fact, the wound repair mechanisms are regulated via VEGF which is both expressed by epithelial cells of salivary glands7 and keratinocytes.6 These are the main sources of VEGF during wound healing, acting in a paracrine and autocrine manner,6 and promoting wound healing via stimulation of endothelial cell-mediated angiogenesis. Thus, clinicians should consider sunitinib as a trigger to oral mucositis.

Sunitinib adverse event: oral bullous and lichenoid mucositis / Mignogna, MICHELE DAVIDE; Fortuna, Giulio; Leuci, Stefania; Pollio, Anna; Ruoppo, Elvira. - In: THE ANNALS OF PHARMACOTHERAPY. - ISSN 1060-0280. - ELETTRONICO. - (2009), pp. 546-547.

Sunitinib adverse event: oral bullous and lichenoid mucositis

MIGNOGNA, MICHELE DAVIDE;FORTUNA, GIULIO;LEUCI, STEFANIA;POLLIO, ANNA;RUOPPO, ELVIRA
2009

Abstract

Sunitinib is an oral, multi-targeted tyrosine kinase inhibitor that inhibits the vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor (PDGFR), the stem cell factor receptor (SCF or c-Kit), and the colony-stimulating factor-1 receptor.1 It was approved for the treatment of renal and gastrointestinal stromal tumors2 and also recently showed anti-tumor activity in patients with metastatic breast cancer.1 This case is the first to describe the oral clinical aspects of sunitinib-suspected oral mucositis toxicity in a breast cancer patient. Although the frequency of grade 3/4 toxicities occurring with Sunitinib is relatively low (< 10%), mostly reported in renal cell cancer rather than metastatic breast cancer studies, the oral adverse event, always described as stomatitis or mucositis, occurred with varying frequency nonetheless (10-30%).3 This case is unique because for the first time it describes the oral clinical aspects of sunitinib-induced stomatitis, characterized by bullous and erosive lesions with widespread lichenoid and necrotizing areas which appeared 12 hours after the second day of the third cycle. She discontinued sunitinib and received prednisone (25 mg PO qd) for three days, followed by topical corticosteroids such as mouthwash bid for seven days. The patient was counseled to modify her diet regimen, eat soft foods, drink non-alcoholic liquids with a straw, and to maintain meticulous oral hygiene by using a toothbrush with soft bristles and a diluted solution of chlorexidine 0.12% as a mouthwash in case of bleeding gums.3 Ten days later she was in complete clinical remission. The patient was not re-challenge, because she refused to take the medication again. Although the first target of sunitinib is the capillary endothelium which blocks VEGFR 1/2/3, PDGFR, c-Kit and Flt-3 (FMS-like tyrosine kinase 3), the presence of these receptors has also been detected in other tissue, e.g., c-Kit in the acini and ducts of salivary glands,4 in human keratinocytes,5 and VEGFR-1 in the epidermal layer of unwounded skin. It is likely that the initial damage induced by suninib in the oral cavity may affect not only vascular tissue, but even salivary glands and keratinocytes. Once the damage is established, these lesions might self-maintain, due to an impairment of wound healing mechanisms. In fact, the wound repair mechanisms are regulated via VEGF which is both expressed by epithelial cells of salivary glands7 and keratinocytes.6 These are the main sources of VEGF during wound healing, acting in a paracrine and autocrine manner,6 and promoting wound healing via stimulation of endothelial cell-mediated angiogenesis. Thus, clinicians should consider sunitinib as a trigger to oral mucositis.
2009
Sunitinib adverse event: oral bullous and lichenoid mucositis / Mignogna, MICHELE DAVIDE; Fortuna, Giulio; Leuci, Stefania; Pollio, Anna; Ruoppo, Elvira. - In: THE ANNALS OF PHARMACOTHERAPY. - ISSN 1060-0280. - ELETTRONICO. - (2009), pp. 546-547.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/375789
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