Safety of the Off-Label Use of Antitumor Drugs in Real Clinical Practice: Experience of Oncologists of the Russian Federation

Introduction . One of the key issues associated with the off-label use of antitumor drugs is safety. Typically, the advantages of such prescriptions in oncology are linked to the potential clinical benefits outweighing the risks of complications. Aim . To assess the safety of the off-label antitumor drug therapy in comparison with the on-label drug administration in the context of real clinical practice among oncologists in the Tula region. Materials and methods . The study was conducted at the Tula Regional Clinical Oncology Center, Russia. Over a six-month period in 2019, clinical data, provided by the regional information system, were analyzed for 919 completed treatment cases of 201 patients over 18 years of age who received antitumor drug therapy for malignant neoplasms. The study enrolled patients who had at least one hospitalization and got off-label antitumor drug therapy, as well as those receiving on-label drug treatment. The study assessed the safety of the off-label antitumor drug therapy in comparison with that of the on-label treatment, estimating the frequency of adverse events (AEs), spectrum of adverse events, severity of adverse events, fatal outcomes, treatment delays and discontinuations, and hospitalizations due to toxicity. A comparative analysis involved the results of using off-label and on-label antitumor drug therapy in terms of the aforementioned parameters. Results and discussion. No unforeseen adverse events were revealed in the study. The spectrum of adverse events encompassed 40 clinical and laboratory abnormalities with varying frequencies across the studied groups. Adverse events were observed in the majority of patients across both studied groups (83% and 86%). A predominance of grade I and II toxicity was noted. In some instances, therapy was discontinued and treatment was suspended; however, the frequency of these occurrences was significantly lower compared to current literature data. One fatal outcome due to complications from the administered therapy was recorded. All adverse events were reported in both studied groups with similar frequencies. The most commonly observed adverse events in both groups included hepatotoxicity, anemia, thrombocytopenia, nephropathy, cephalalgia, leukocytosis, skin toxicity, dyslipidemia, hypertension, bone pain syndrome, and dizziness. Other adverse events occurred sporadically with similar frequency. The most severe presentations were noted in the following adverse events: thrombocytopenia, gastrointestinal toxicity, leukocytosis, hyperglycemia, and immune-mediated diabetes mellitus with ketoacidotic coma. Conclusion . In real clinical practice, the safety of off-label and on-label antitumor drug therapy reveals no significant difference.