Adverse drug reactions in oncoLogy: intEnsive monitoring program on biotechnological anD taRget therapies in Oncologic patientS-ALEXANDROS observational study

Introduction: Oncologic patients are particularly susceptible to adverse drug reactions (ADRs) [1]. Their sensitivity to ADRs results from: narrow therapeutic index of some chemotherapeutics, multidrug regimens and comorbidities. Malnutrition and organ dysfunctions could also affect drug pharmacokinetics making drug safety less predictable [2]. Therefore, monitoring oncologic patients’ safety in clinical practice should be a priority [3]. Aim: To evaluate occurrence of ADRs and potential drug-drug interactions (DDIs) associated to antineoplastic target therapies. Methods: A retrospective, observational, no-profit study (ALEXANDROS), was carried out at the Unit of Oncology of the University Hospital in Florence. Adult patients accessing from July 2014 to July 2016 with target therapies for solid tumour indications (Anatomical Therapeutic Classifications: L01XC-monoclonal antibodies; L01XE-protein kinase inhibitors) were included. Patients’ data were retrieved from medical records using the Patient Data Form available on Pharmacowikilance (a platform developed by the Tuscan Regional Centre of Pharmacovigilance), including demographic information, medical history, pharmacological treatments, and ADRs. Potential DDIs were assessed by checking DDIs on Micromedex. Results: Overall, 130 Caucasian cancer patients, mean age 64.28 years (standard deviation, SD ± 12.12), with the following primary cancer diagnosis: 39 colorectal cancer, 27 lung cancer, 26 breast cancer, 25 ovarian cancer, 8 kidney cancer, 3 gastric cancer and 2 hepatic cancer, were included. The mean number of drugs/patient was 7.27 (SD ± 4.5). Adverse events and ADRs were 234 and 223 respectively (105 patients had at least one ADR, range 1–8 ADRs/patient). Among the 223 ADRs, 27 were serious (21 patients had at least one serious ADR, range 1–3 serious ADRs/patient) and 10.31% were unexpected. The most frequently reported ADRs (at least 5 cases for single ADR) were: cutaneous toxicity (n = 31), diarrhoea (n = 27), neutropenia (n = 23), mucositis (n = 18), nausea (n = 15), hypertension (n = 15), palmar-plantar erythrodysesthesia (n = 11), asthenia (n = 10), hypertransaminasemia (n = 5). ADR outcomes were: resolved (41.29% of cases), resolving (39.35%), not resolved (8.39%), not specified (7.09%) and resolved with sequalae (3.87%). The most frequently combinations of suspected drug-ADR were: bevacizumab-neutropenia (n = 15); bevacizumab-nausea (n = 10); bevacizumab-diarrhoea (n = 6); bevacizumab-hypertension (n = 5); cetuximab-cutaneous toxicity (n = 9); erlotinib-cutaneous toxicity (n = 17); erlotinib-diarrhoea (n = 5); and erlotinib-mucositis (n = 5). The identified DDIs were: erlotinib-esomeprazole (n = 1); erlotinib-lansoprazole (n = 13); erlotinib-magaldrate (n = 6); erlotinib-omeprazole (n = 6); erlotinib-pantoprazole (n = 7); gefitinib-lansoprazole (n = 1); sunitinib-sotalol (n = 2). None of these resulted in expected ADRs. Discussion: The sensitization of drug safety may be improved especially in the oncological setting. Conclusion: Drug safety monitoring in cancer patients is a priority issue. Healthcare professionals should be adequately stimulated in detection and reporting of ADRs.