Laface Carmelo, Scartozzi Luca, Pisano Chiara, Vanella Paola, Greco Antonio, Vaiano Agostino Salvatore, Numico Gianmauro
Medical Oncology, AO S. Croce e Carle, 12100 Cuneo, Italy.
Institute of Ophthalmology, Santa Croce e Carle Hospital, 12100 Cuneo, Italy.
J Clin Med. 2025 Jun 8;14(12):4052. doi: 10.3390/jcm14124052.
Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible for various adverse events (AEs), in particular hepatic and dermatological AEs. To date, limited data are available in the literature regarding ocular AEs due to therapy with these drugs. In this regard, one case of corneal perforation during treatment with a VEGFR-TKI, Regorafenib, has been reported, while there are no data about Cabozantinib. In this paper, we present another clinical case of corneal perforation in a patient affected by advanced RCC and treated with Cabozantinib as a second-line therapy. The patient started Cabozantinib at the dosage of 60 mg/die although it was necessary to apply some dose reductions because of grade 2 AEs (according to CTCAE v6.0), such as asthenia, diarrhea, dysgeusia, and loss of appetite. After approximately 15 months of treatment, the patient began to experience pain and vision loss in the right eye. A diagnosis of corneal perforation was made, followed by medical and surgical treatment. As regards the etiology of this pathology, all other possible causes were excluded, including a history of ocular disease, contact trauma, exposure to damaging agents (e.g., chemical agents and prolonged use of drugs such as topical NSAIDs), infections, or dry eye. Therefore, we hypothesized a correlation with Cabozantinib's mechanisms of action and paused its administration. Cabozantinib may alter the ocular environment due to a lack of or imbalance in growth factors in the tear film, with a reduction in corneal epithelium proliferation. This condition might cause dry eye and a delay in corneal healing. Therefore, particular importance should be placed on ophthalmologic surveillance during treatment with these drugs in patients who develop ocular symptoms. Further in vitro and in vivo studies are necessary to deepen the knowledge about VEGFR-TKI-mediated ocular AEs.
卡博替尼是一种血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKI）。这些药物被用于多种恶性肿瘤的治疗。具体而言，卡博替尼已证明其对多种恶性肿瘤有效。另一方面，卡博替尼和其他VEGFR-TKIs可能会导致各种不良事件（AE），尤其是肝脏和皮肤方面的AE。迄今为止，关于这些药物治疗引起的眼部AE，文献中的数据有限。在这方面，有报道称1例使用VEGFR-TKI瑞戈非尼治疗期间发生角膜穿孔的病例，而关于卡博替尼则没有相关数据。在本文中，我们报告了另一例晚期肾细胞癌患者使用卡博替尼作为二线治疗时发生角膜穿孔的临床病例。患者开始以60mg/天的剂量服用卡博替尼，不过由于出现2级AE（根据CTCAE v6.0），如乏力、腹泻、味觉障碍和食欲不振，有必要进行一些剂量调整。治疗约15个月后，患者右眼开始出现疼痛和视力丧失。诊断为角膜穿孔，随后进行了药物和手术治疗。关于这种病理的病因，排除了所有其他可能的原因，包括眼部疾病史、接触性创伤、接触损伤性物质（如化学物质和长期使用局部非甾体抗炎药等药物）、感染或干眼。因此，我们推测与卡博替尼的作用机制有关，并暂停了其给药。卡博替尼可能由于泪膜中生长因子缺乏或失衡而改变眼部环境，导致角膜上皮增殖减少。这种情况可能会导致干眼和角膜愈合延迟。因此，对于出现眼部症状的患者，在使用这些药物治疗期间应特别重视眼科监测。需要进一步的体外和体内研究来加深对VEGFR-TKI介导的眼部AE的认识。
