Painful oral aphthous-like lesions in patient with kidney cancer after target therapy and bisphosphonate administration: a case report of adverse drug reaction.

Aim. Tyrosine kinase inhibitors (TKIs) targeting tu- mor angiogenesis and mammalian target of rapamycin inhibitors (mTOR) are indicated for the management of several cancer types, as for renal cell carcinoma (RCC). Oral ulcerations are reported as common adverse drug reactions of mTOR inhibitors and are currently classified as mTOR inhibitor associated stomatitis (mIAS). Interestingly, these lesions appear as aphthous-like stoma- titis rather than the mucositis seen with chemotherapy agent. Case report. A 49 years old male patient underwent to the left radical nephrectomy in May 2014 for clear RCC. From July to October 2014 he was treated with Pazopanib, a tyrosine kinase inhibitor. In December 2014 the patient started the treatment with Zoledronic acid and Everolimus, an amino-bisphosphonates and an mTOR inhibitor, respectively. Everolimus administration was suspended on the 1st of January 2015 and resumed on the 4th of February. In February 2015, the patient referred to our department for acute pain of mouth floor and tongue; the onset of these symptoms was subse- quent to mTOR therapy. This pain compromised his oral functions (chewing, swallowing, phonetic) and quality of life. Intraoral examination showed aphthous-like lesions on both borders of the tongue and on the right side of the mouth floor. Local antiseptic (0.2% chlorhexidine rinse, twice daily for 1 week), 0.050 g clobetasol propionate cream (twice a day for 4 week, and one times a day for the following 4 weeks) and a wound-healing promoter (Mucosamin Spray®, twice a day for 2 weeks) were administered. Since the oncologist decided to not discontinue the target therapy, the patient continued local therapy until the end of the treatment with everolimus. After two weeks from the first visit, a complete healing of the oral mucosa was observed and the patient complained no pain. Conclusion. This case report confirms the recent view that target therapy with everolimus may induce the onset of aphthous-like stomatitis as adverse drug reaction. Therefore, diagnostic algorithms for stomatitis should include a careful drug history, emphasizing the focus also on oral adverse effects the new target cancer therapies.