DISCUSSION
Wexner constipation, toxicity, cancer, cancer pain, pain, constipation, hypertension
ADVERSE REACTIONS, ADVERSE EVENTS, CANCER, ADVANCED CANCER, MINOR, DISORDERS, ADVERSE EFFECTS, HYPERTENSION
As far as we know, this is the first randomized controlled clinical trial to study the effects of an oral magnesium compound on opioid analgesia in patients with cancer pain. A systematic review has summarized the intravenous use of magnesium compounds (mainly MgSOOur results revealed that although the opioid dosage of the two groups continued to increase, a safe daily oral dose of L‐TAMS (1.5 g or 2.0 g/day) significantly reduced the increase in opioids in patients with advanced cancer compared with the placebo group starting on day 30. On day 90, this difference was even more pronounced. This is consistent with the conclusion that magnesium can reduce the dosage of opioids and ease the development of opioid tolerance.The mechanism of the effect of MgMoreover, it was observed in our study that constipation in the L‐TAMS group was significantly relieved compared to that in the placebo group on day 7. The adjusted Wexner constipation score in the L‐TAMS group continued to decrease until day 21, while the Wexner score in the placebo group was not significantly improved. In addition to the classic osmotic cathartic effect of magnesium salts,There were no significant differences in VAS score or the frequency of BTcP between the two groups, but it is interesting to note that the VAS scores of the two groups all declined from baseline, and we assume that some of the patients did not have enough pain relief before this trial began. Although L‐TAMS can help reduce morphine dosage and ease the development of opioid tolerance, prescribed opioid dosage often fails to meet the analgesic needs of some advanced cancer patients orally. There were no significant differences in PHQ‐9 and GAD‐7 scores between the two groups, suggesting that oral L‐TAMS cannot relieve mental disorders in patients with advanced cancer. We did not find statistically significant differences between the two groups in other adverse events except for constipation. On the whole, this dosage of L‐TAMS is safe. A systematic review of studies on oral magnesium preparation for the treatment of hypertension showed that no severe adverse reactions were observed after oral doses equivalent to as much as 972 mg magnesium per day, which was much higher than our trial dosage, and most reported adverse effects were minor and transient.Our trial had some limitations. First, because of the complexity of participants' pain and the lack of similar references, there were no exact criteria for dose escalation in this trial, which needs to be improved in subsequent studies. Second, our results suggested that the effect of L‐TAMS on morphine tolerance may be slow, but at the same time, paradoxically, patients with advanced cancer do not allow us to set excessively long data collection timelines. Third, we did not measure patients' blood magnesium levels or their changes. However, a long period of clinical experience has shown that serum magnesium concentration does not reflect its concentration in other tissues in a repeatable and credible method,In conclusion, our study shows that safe oral dosage of L‐TAMS can improve the analgesic effect of opioids and reduce the dosage of opioids used in patients with advanced cancer while significantly relieving OIC without significant toxicity or side effects. More clinical samples and longer follow‐up period are necessary to determine the impact of oral L‐TAMS on opioid tolerance in cancer patients.