RT Journal Article
SR Electronic
T1 Effect of Perioperative Lidocaine and Cisplatin on Metastasis in a Murine Model of Breast Cancer Surgery
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5599
OP 5606
DO 10.21873/anticanres.12894
VO 38
IS 10
A1 JAMES FREEMAN
A1 PETER D. CROWLEY
A1 ANDREW G. FOLEY
A1 HELEN C. GALLAGHER
A1 MASAE IWASAKI
A1 DAQING MA
A1 DONAL J. BUGGY
YR 2018
UL http://ar.iiarjournals.org/content/38/10/5599.abstract
AB Background/Aim: Mortality from breast cancer is usually attributable to metastasis. In vitro data suggest that amide local anaesthetics, e.g. lidocaine, inhibit metastasis by multiple mechanisms and recent in vivo data support this. Experimental data also suggest that opioids may inhibit cisplatin chemotherapy. Whether lidocaine would influence cisplatin chemotherapy has not been evaluated. Materials and Methods: 4T1 cells were injected into the mammary gland of immunocompetent female BALB/c mice, with resection of the tumour under sevoflurane anaesthesia one week later. Mice (n=45) were randomized into one of three groups: The cisplatin group received 3 mg.kg−1 cisplatin; cisplatin and lidocaine group received 3 mg.kg−1 cisplatin and lidocaine bolus of 1.5 mg.kg−1 followed by an infusion of 2 mg.kg-1.h−1. The control group received sevoflurane only. All agents were given perioperatively. After 14 postoperative days, post-mortem lung, serum and liver samples were collected. Primary outcome measure was lung metastasis colony count. Results: During sevoflurane anaesthesia, the addition of lidocaine to cisplatin significantly decreased metastatic lung colony count [(mean±SD) (157±87)] compared to control [846±581, (p=0.001)], and cisplatin alone [580±383, (p=0.018)]. However, liver metastasis colony count was not reduced with the combination of cisplatin and lidocaine (9.3±13.9) when compared to control (74.7±257.3), p=0.78 or to cisplatin alone (110±388.8), p=0.569. Serum VEGF and interleukin-6 concentrations were not significantly different. Conclusion: In a 4T1 murine model of breast cancer surgery, under sevoflurane anaesthesia, lidocaine enhanced the metastasis-inhibiting action of cisplatin. Clinical evaluation of the hypothesis that co-administration of systemic lidocaine during cisplatin chemotherapy seems warranted.