Does perioperative i.v. lidocaine infusion during tumour resection surgery reduce metastatic disease in the 4T1 mouse model of breast cancer?

Abstract

Background: Compelling in vitro data exists that amide local anaesthetics (ALAs) inhibit cancer cell biology and metastatic potential in a variety of tumours. Prior to undertaking prospective, randomised clinical trials on the effect of ALAs on oncological surgery outcomes, in vivo data are required. No previous in vivo data addressing this question exists. Methods: We optimised the 4T1 BALB/c mouse model of cancer. Day 0: n=72 BALB/c mice were inoculated with 25 000 4T1 cancer cells in the mammary fat pad. Day 7: mice were randomised and the tumour was resected under inhalational sevoflurane or intraperitoneal (i.p.) ketamine/xylazine anaesthesia with or without i.v. lidocaine, 1.5 mg kg−1 bolus followed by 2 mg kg−1 hr−1 infusion for 20 minutes. Day 21: mice euthanised and lung tissue cultured in medium that selects metastatic cells. Day 35: colonies counted. Results: There was no difference between the initial tumour size in the lidocaine and control groups. There was significant reduction in the number of mice that had any detectable pulmonary metastatic disease in the sevoflurane/lidocaine vs sevoflurane group, 28% vs 54%, (P=0.04) and a significant reduction in the median pulmonary metastasis colony counts (0 vs 22, respectively, P=0.02). In the i.p. ketamine/xylazine/lidocaine group, 100% animals had pulmonary metastasis vs 60% control animals (P=0.02). Conclusions: In the 4T1 mouse model of breast cancer, perioperative i.v. lidocaine reduced metastasis after sevoflurane anaesthesia, but increased metastasis with ketamine/xylazine anaesthesia. This suggests the anti-metastatic potential of lidocaine may be altered by anaesthetic agents in vivo. Further studies are warranted to evaluate this. This study was approved by the UCD Animal Research ethics Committee and the Health Products Regulatory authority.