Negative influence of morphine on the efficacy of interleukin-2 cancer immunotherapy

Opioid substances have been proven to determine immunosuppression and in pa rticular to inhibit interleukin-2 (IL-2)-induced antitumor immune response. However, despite the large number of experimental studies showing the immu nosuppressive role of opioids, the real clinical impact of opioid therapy d uring IL-2 cancer immunotherapy is still obscure. The present study was per formed to analyze the influence of a concomitant therapy for pain with the mu-opioid agonist morphine or with the kappa-opioid agonist buprenorphine o n the effectiveness of IL-2 as an antitumor immunotherapy. The study was ca rried out in 85 metastatic renal cell cancer patients. IL-2 was given subcu taneously at a daily dose of 6 million IU for 5 days/week for 6 weeks. Twen ty-two patients received buprenorphine and;18 patients received morphine. T he remaining 45 patients received either no antalgic drug or nonsteroidal a ntiinflammatory agents. The response rate was significantly higher in patie nts who did not receive opioids than in those treated either with morphine or with buprenorphine. Similarly the percentage of 1-year survival was sign ificantly higher in opioid-free patients than in those treated with morphin e or with buprenorphine. In contrast, no significant differences were seen in IL-2-induced cardiovascular toxicity This preliminary study confirms the negative influence of opioids on IL-2 induced anticancer efficacy in human s, at least in metastatic renal cell cancer.