Effect of clonidine on oncological outcomes after breast and lung cancer surgery

Abstract

We read with great interest the paper by Lavon and colleagues1Lavon H. Matzner P. Benbenishty A. et al.Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.Br J Anaesth. 2018; 120: 188-196Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar on the dose-dependent effects of dexmedetomidine in animal models of breast, lung, and colon cancers. The authors report an increased metastatic burden in these models with the use of high doses of dexmedetomidine, but not with low, sub-hypnotic doses. Even a beneficial effect was found with sub-hypnotic doses of dexmedetomidine in one stress paradigm. As alpha-2 agonists are mostly used as adjuvants during surgery at sub-hypnotics doses, the implications of human data would be of prime importance. This is particularly relevant as alpha-2 agonists are potential components of opioid-free anaesthesia, and opioids are under investigation for their tumour-growth promoting effect.2Forget P. Collet V. Lavand'homme P. De Kock M. Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages.Eur J Anaesthesiol. 2010; 27: 233-240Crossref PubMed Scopus (76) Google Scholar To investigate the implication in the clinic, we performed a sub-analysis of previously published series of breast and lung surgical cancer patients.3Forget P. Machiels J.P. Coulie P.G. et al.Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery.Ann Surg Oncol. 2013; 20: S650-S660Crossref PubMed Scopus (121) Google Scholar The potential association of another alpha-2 agonist, clonidine, widely used during surgery, was studied. Briefly, 323 patients underwent curative breast cancer surgery with mastectomy and axillary clearance. When used, a median dose of 150 μg clonidine i.v. was administered (n=188). Overall, 334 lung cancer patients underwent curative-intended resection for primary stage I or II non-small cell lung cancer. The same median dose of clonidine was used (n=49). No difference was detected in risk factors between the groups, both in breast and lung cancer patients. The endpoints were recurrence-free and overall survival; Kaplan–Meier analyses were used to estimate these endpoints. After univariate analysis, a Cox regression model was used for (adjusted) multivariable analyses while adjusting for any already identified risk factors. Approval was obtained from the Ethical Committee N/REF 2010/15MAR/085, N#B40320108384; CEBH of the Universite catholique de Louvain, Brussels, Belgium. The results showed that clonidine was not associated with shorter recurrence-free or overall survival, after both breast and lung cancer surgeries (Fig. 1 and Supplementary material). This is in accordance with previous published data with clonidine, showing a protective effect.2Forget P. Collet V. Lavand'homme P. De Kock M. Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages.Eur J Anaesthesiol. 2010; 27: 233-240Crossref PubMed Scopus (76) Google Scholar Taken together, these reassuring data regarding sub-hypnotic doses of alpha-2 agonists, or at least clonidine, should lead us to cautiously avoid any premature conclusion about the effect of these important medications. The authors declare that they have no conflicts of interest. The following is the supplementary data related to this article: Download .docx (.03 MB) Help with docx files Multimedia component 1 Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancersBritish Journal of AnaesthesiaVol. 120Issue 1PreviewPerioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use on cancer metastatic progression. Full-Text PDF Open Archive