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Background: Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications. Methods: A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture in vitro, in vivo, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies. Results: Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. In vitro studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of in vitro studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported. Conclusions: Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together. Clinical trial registration: Open Science Framework (OSF, project link: https://osf.io/r2u4z).
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PURPOSE OF REVIEW: Cancer is a leading cause of death worldwide, and incidence is increasing. Excisional surgery is essential in approximately 70% of solid organ tumours. Emerging research in onco-anaesthesiology suggests that perioperative anaesthetic and analgesic techniques might influence long-term oncologic outcomes. RECENT FINDINGS: Prospective, randomized control trials (RCTs) demonstrate that perioperative regional and neuraxial anaesthetic techniques do not affect cancer recurrence. Ongoing trials are investigating the potential outcome benefits of systemic lidocaine. Retrospective studies indicate improved postoperative oncologic outcomes for certain types of breast cancer with higher intraoperative opioid dosage, nuancing available evidence on the effect of opioids. RCT evidence suggests that propofol has no beneficial effect compared with volatiles on breast cancer recurrence, although it remains unclear whether this applies to other cancer types. SUMMARY: Although regional anaesthesia definitively does not affect cancer recurrence, ongoing prospective RCTs with oncological outcomes as primary endpoints are awaited to establish if other anaesthetic or analgesic techniques influence cancer recurrence. Until such trials conclusively identify a causal relationship, insufficient evidence exists to recommend specific anaesthetic or analgesic techniques for tumour resection surgery based on altering the patient's risk of recurrence.