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.