We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30–35 mg/m2 twice daily on days 1–5 and days 8–12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2–15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months’ follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4–5.1) months and median OS was 9.3 (95% CI 6.6–12.1) months. The most common grade 3–4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.

BackgroundCeritinib is indicated for the treatment of adult patients with non-small cell lung cancer (NSCLC), when the disease is advanced, the patient is anaplastic lymphoma kinase (ALK) positive and the disease has been treated previously with crizotinib. The data sheet for ceritinib describes hepatotoxicity as an uncommon adverse reaction observed in less than 1% of patients in clinical trials. In addition, ceritinib is on the European list of medicinal products under additional monitoring.PurposeTo describe a case of severe hepatotoxicity in a patient with advanced NSCLC treated with ceritinib.Material and methodsThis was a descriptive and retrospective clinical case. Data were obtained by review of the electronic medical records.ResultsA 57-year-old man was followed by the oncology service for an ALK positive advanced NSCLC. He had received treatment with crizotinib 250 mg twice a day from November 2015 to June 2016 when this treatment was interrupted because of disease progression which was determined by imaging tests.Consequently, ceritinib treatment was started in June 2016 with a daily dose of 750 mg. Before starting this medication, laboratory hepatic parameters were controlled (including AST, ALT and total bilirubin), as indicated in the data sheet, and all were in normal range. A month later, there was a marked elevation in transaminases: GPT 455 (grade 3), GOT 123 (grade 2), GGT 721, alkaline phosphatase 662. Ceritinib was discontinued and transaminases started to decrease. The Karch–Lasagna algorithm established a ‘probable’ relationship between hepatotoxicity and ceritinib based on temporal correlation of the facts and the apparent lack of another perpetrator of hepatic damage.ConclusionDrug induced hepatic injury is one of the most common reasons for withdrawal of an approved drug. For this reason, health professionals must be vigilant in identifying drug related liver injury, especially those related to drugs on the European list of medicinal products under additional monitoring. In our case, hepatic transaminases increased progressively throughout the course of the treatment with ceritinib and have continuously decreased since ceritinib discontinuation. This adverse reaction was reported to the national pharmacovigilance system.References and/or acknowledgementsEuropean list of medicinal products under additional monitoring. September 2016.No conflict of interest

BackgroundPembrolizumab is a selective humanised IgG4 monoclonal antibody known as a programmed cell death 1 (PD-1) immune checkpoint inhibitor. It is the first PD-1 Inhibitor approved for unresectable or metastatic melanoma. With the arrival of this new mechanism of action, immune mediated adverse reactions have also been detected.PurposeTo describe immune mediated nephritis in a diagnosed nodular melanoma patient, treated with pembrolizumab as a secondline treatment.Material and methodsData were obtained by review of the electronic medical records.ResultsA 78-year-old man had a BRAF mutated metastatic nodular melanoma. He was included in the Columbus clinical trial and received a combination of BRAF inhibitor and MEK inhibitor as firstline treatment from April to September 2015. At that time, disease progression was determined by imaging tests. In October, the lesion was operated and patient received radiotherapy for 4 months. In March 2016, pembrolizumab was started as a secondline treatment, and was well tolerated at the beginning (cycles 1 and 2). After cycle 3, creatinine started to increase, reaching 3.59 (grade 3), and estimated glomerular filtration rate was 17.57 mL/min/1.73 m2. These laboratory abnormalities caused the patient’s emergency admission to hospital and treatment discontinuation. Renal function analytical parameters decreased to the normal range a month after treatment discontinuation.Nephritis occurred in 0.4% of patients receiving pembrolizumab in the Trials keynote 001, 002 and 003. The median time to onset of nephritis was 5.1 months (range 12 days to 12.8 months). The Karch–Lasagna algorithm established a ‘possible’ relationship between nephritis and pembrolizumab treatment due to the existence of a temporal correlation between the facts.ConclusionHealth professionals must be vigilant in identifying drug related adverse reactions, particularly those related to drugs on the European list of medicinal products under additional monitoring. Nephritis has been reported in patients receiving pembrolizumab, and consequently patients should be monitored for changes in renal function, and other causes of renal dysfunction should be excluded. In our case, creatinine dramatically increased after the third cycle of treatment with pembrolizumab (onset of 3 months) and it has continuously decreased since pembrolizumab discontinuation, eventually reaching the normal range. This adverse reaction was reported to the national pharmacovigilance system.References and/or acknowledgementsEuropean list of medicinal products under additional monitoring, 2016.No conflict of interest

excellent if £5%. From 2016 to 2019 an audit was carried out annually, selecting a random sample of 30 patients and establishing an annual improvement plan according to the results (Table 1).The improvement proposals established for each year were: 2016, include a week rotation in the reconciliation area for the first-year resident; 2017, extend MR rotation of the thirdyear resident from 2 to 5 months; 2018, establish a supervision/review circuit by the reference pharmacist of the RRs performed.

Background The Pharmacy and Haematology units, together with the hospital management, implemented a system for the dispensing of low molecular weight heparins (LMWH) for patients treated for anticoagulation with acenocoumarol and awaiting minor outpatient surgery. Purpose To evaluate the implementation of this protocol, and to quantify its financial impact. Materials and methods Retrospective observational study of 100% of the patients included in 2012. Data obtained: number of patients, demographic data and number of units LMWH dispensed. For the cost calculation, the differential cost was used between the acquisition cost and cost per prescription. We also took into account the number of units left over at home if the LMWH had been acquired by prescription. Results A total of 591 patients were included (mean age 71.83 ± 11.65). A total of 4,637 doses of LMWH were dispensed (mean 7.84 ± 1.98 days’ treatment per patient), all of which were accompanied by verbal and written information. Introducing this system simplified the acquisition of LMWH and reinforced the information given to the patients. It also streamlined the haematology consultations and avoided having to suspend scheduled surgery due to a failure to adhere to or understand the treatment. The new system saved 46,298 euros during the study period. The number of excess units if they had been acquired by prescription would have been 1,325 units. Dispensing the precise number of units helped to prevent possible medicines errors. Conclusions The new system ensures that patients understand their instructions and reinforces compliance, as well as providing significant savings for the healthcare authorities. The results of implementing this system reaffirm the validity of multidisciplinary working protocols of this kind in order to optimise available resources. No conflict of interest.