CASE DESCRIPTION
A  72-year-old woman with smoking and epilepsy history was diagnosed from a stage pT3a renal carcinoma in December 2015. Radical right nephrectomy was performed in February 2016 and oncological follow-up was performed every 3 months. In September 2018, a right lung segmentectomy was practiced due to lepidic adenocarcinoma growth. Post-surgical changes included right atelectasis, pleural effusion and a right hilar adenopathy of 16 x 13 ml was detected. Two and a half years later, on February 2021 progression was detected with right adrenal massive bleeding, hilar adenopathy and left renal adrenal metastasis. In May 2021, treatment with nivolumab for intermediate-risk clear-cell renal carcinoma was initiated achieving stabilization of the tumour. Treatment was well-tolerated, despite dry mouth, grade II anorexia and grade I astheny, without immune-mediated toxicities found. However, a new progression was detected and oral treatment with cabozantinib 60 mg daily was initiated as second line treatment in December 2021.Secondary to treatment, patient had grade I hypertension, and also referred nausea and grade I diarrhoea, so treatment with enalapril 5mg c/24h was prescribed, but no reduction in cabozantinib dose was needed. A new progression of cancer was detected and third line treatment with everolimus at 10 mg/daily in fasted conditions (1 hour before breakfast) was started in the 21st of March, 2022.
Before any oral cancer treatment initiation, patient chronic medication plan is reviewed by the hospital pharmacist as part of pharmaceutical care provided. On this occasion, treatment included Carbamazepine 400mg every 12hours, Phenytoin 100mg every 12 hours and Acetaminophen 650mg plus Tramadol 75mg every 8 hours. Drug interaction checking was performed, using two databases (Lexicomp and Drugs). As a result, a joined interaction of everolimus with both antieleptic drugs was detected. Carbamazepine and Phenytoin are classified as strong CYP3A4 inducers and could lead to decreased everolimus Cminss and diminish its efficacy. According to this finding, after multidisciplinary discussion within the oncologist and the pharmacist, a TDM was suggested and planned, and blood samples were obtained immediately before everolimus administration in 20th April. Method used for analysis was ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. TDM result showed a Cminss of 3.7ng/ml which was considered as an underexposure to everolimus .
Adherence to treatment was reinforced to patient and, since patient didn’t have any relevant toxicities, pharmacist suggested an everolimus dose increase from 10 mg to 15 mg daily (administered 10 mg, 1-hour before breakfast and 5 mg, 1-hour before dinner) which was agreed with patient’s oncologist. A second TDM was scheduled in 16th of May and showed that Cminss had increased from 3.7 to 6.4 ng/ml, without relevant toxicities. A second dose adjustment was made, and dose was increased once again until 10mg every 12 hours, administered before meals. Two-weeks and a month later, new TDM were planned and Cminss observed were 10.6ng/ml and 8.7ng/ml, respectively (Figure I). During everolimus treatment, stable disease was achieved, and no relevant toxicities were observed. Unfortunately, everolimus treatment was stopped on July 2022, due to lung progression, pleural effusion, and respiratory insufficiency, and finally patient died one week later.