Effects of opioids on tumour growth and metastasis in animal models: a systematic review.

BACKGROUND

The International Agency for Cancer Research monographs recently classified opium consumption as carcinogenic to humans, with sufficient evidence for carcinogenicity in the larynx, lung, and urinary bladder and limited evidence in the oesophagus, pancreas, stomach, and pharynx. This causes concerns of a potential cancer-promoting effect in the same organs associated with the use of pharmaceutical opioids.

METHODS

We performed a systematic review (registered in the Open Science Framework: osf.io/xyg9p) of the published in vivo preclinical literature to determine whether the effects of opioids on tumour growth and metastasis are organ specific. We investigated whether the opioid category (agonist, antagonist, or peptide), organ of origin of the cancer cells, site of tumour measurement, immune status of rodents, opioid dose, or duration of opioid exposure was associated with reported cancer outcomes.

RESULTS

A total of 118 studies, representing 168 experiments, were included. Most animal experiments (94/168, 56%) reported an anti-cancer effect of opioids and 31 (18%) reported a pro-cancer effect. Of the assessed parameters, opioid category (P<0.001) and opioid dose (P=0.0056) were the only factors significantly associated with the reported cancer outcome. In studies testing morphine, experiments showing a cancer-promoting effect predominantly administered low doses of morphine (the proportion of studies using low-dose morphine was 65% among those reporting pro-cancer outcomes vs 8% among those reporting anti-cancer outcomes).

CONCLUSIONS

We found no relationship indicative of an organ-specific, cancer-promoting effect of opioids.