A Combination of Beta-Adrenergic Antagonist and Cyclooxygenase-2 Inhibitor Improves Survival Rates in Murine Models of Postoperative Metastasis

A Combination of Beta-Adrenergic Antagonist and Cyclooxygenase-2 Inhibitor Improves Survival Rates in Murine Models of Postoperative Metastasis

A study published in the Journal of Immunology suggests that the combined blockade of excess release of catecholamines (CAs) and prostaglandins (PGs) in cancer patients undergoing tumor excision might improve survival rates and prevent cancer recurrence.

The surgical procedure, a common step in the treatment of most solid cancers, has long been suspected to facilitate the metastatic process, and numerous mechanisms have been implicated.

The study in the Journal of Immunology by Ariella Glasner and colleagues promotes the clinical testing of a new approach for reducing long-term cancer recurrence: blocking excessive perioperative paracrine and neuroendocrine stress responses, and specifically a combined blockade of excess release of CAs and PGs in the perioperative period in cancer patients undergoing tumor excision.

Such an approach has not been tested clinically thus far.

In this study, the authors report that in mice, blocking beta-adrenoreceptors with propranolol and simultaneously inhibiting PG synthesis with etodolac significantly improves recurrence-free survival rates following 3LL or B16 primary tumor excision. These tumors, like most human cancers are poorly immunogenic, expressing no MHC-II and low levels of MHC-I.

Of note, only the combined administration of beta-adrenergic antagonist and cyclooxygenase-2 inhibitor had a significant prophylactic effect in the survival studies.

A possible explanation for this synergism is that during the postoperative period both PG and CA levels are high, and each factor alone can interfere with various immunologic components and pathways and induce suppression of cell-mediated immunity.

This study also indicates that the immediate postoperative period is critical for determining long-term tumor recurrence rates, and that clinical interventions during this time may have substantial long-term benefits.

The authors suggest that drug regimen used in this study may be even more efficient if initiated a few days before surgery, because etodolac could reduce PGs release by primary tumors; propranolol could reduce anxiety and antagonize the excess release of CAs owing to preoperative physiologic and psychologic stress responses.

Overall this can attenuate preoperative suppression of cellular immunity in cancer patients awaiting surgery.

SOURCE: J Immunol 2010, 184: 2449

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