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Abstract Background Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. Methods Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of

Abstract Background Cancer during pregnancy is relatively rare but may lead to maternal mortality. We aimed to assess the incidence of cancer related maternal mortality and the neonatal outcome in these patients. Also, doctor- and patient-related delay in cancer diagnosis and therapy among patients with cancer related maternal mortality is assessed. Methods Maternal mortality was defined as death during pregnancy or within 1 year after delivery. Data of the Dutch Maternal Mortality Committee was used to calculate the cancer related maternal mortality rate and to assess neonatal outcome in the Netherlands. Delay was scored by ten medical specialist based on case descriptions. Results Cancer related maternal mortality rate was 1.23 per 100,000 live births. Delay in either diagnosis or treatment occurred in 65%. Delay in diagnosis was more frequent then delay in treatment, and was mainly caused by health care providers. Only 77% of pregnancies were ongoing, and 65% ended preterm of which 85% was induced. Conclusions Avoiding delay in diagnosis and therapy in case of pregnancy related cancer could potentially improve maternal and neonatal outcome. It is therefore essential to increase awareness among health care providers about the occurrence and recurrence of cancer in pregnancy and the possibilities of diagnostic and therapeutic interventions in these women.

• Scientific evidence on prevention and treatment of opioid-induced constipation (OIC) in cancer patients is limited. • Naldemedine and magnesium oxide are most likely effective for the prevention of OIC in cancer patients. • Oxycodone/naloxone, naldemedine and methylnaltrexone are effective for the treatment of OIC in cancer patients. • Further studies comparing standard laxatives with each other and with opioid antagonists should be conducted before recommendations for clinical practice can be made. Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD −13.68; 95 % CI −18.38 to −8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31–0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64–2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81–5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made. [ABSTRACT FROM AUTHOR]