Purpose: Nausea is a common distressing symptom experienced by advanced cancer patients. This study compared the clinical efficacy of haloperidol to hydroxyzine hydrochloride in combination with haloperidol in the management of nausea induced by continuous infusion of opioids. Methods: This retrospective study comprised 50 advanced cancer patients using continuous infusion of opioids who had been administered either haloperidol alone (haloperidol group) or hydroxyzine hydrochloride with haloperidol (hydroxyzine hydrochloride group); their nausea and characteristics were assessed using multivariate analysis. Results: After the continuous infusion of opioids, nausea occurred in 34% patients in the haloperidol group and 10% patients in the hydroxyzine hydrochloride group. No significant differences were observed in patient characteristics, except for the number of the patients using infusion of opioids. By multivariate analysis, nausea before using continuous infusion of opioids, ileus, and haloperidol without hydroxyzine hydrochloride were extracted as the risk factors of nausea. In both the groups, nausea occurred only in the patients using morphine; nausea occurred in 32.5% patients in the haloperidol group and in 4.5% patients in the hydroxyzine hydrochloride group. Conclusion: Hydroxyzine hydrochloride in combination with haloperidol was observed to be more effective than haloperidol alone in the management of nausea induced by continuous infusion of opioids.

Case 1: A female, aged 81 years, with cardiac stomach cancer. Air retention in the digestive tract aggravated discomfort of the epigastric region, but belching relieved the symptom. As belching insufficiency persisted, the continuous subcutaneous injection of metoclopramide was started. Belching was promoted, and swelling of the upper abdomen was relieved. Case 2: A male aged 57 years. Gastrointestinal obstruction related to pancreatic head cancer was observed. He complained of discomfort of the upper abdomen with abdominal swelling. Belching reduced these symptoms. The continuous subcutaneous injection of metoclopramide facilitated belching, and relieved discomfort of the upper abdomen.Discussion： The results suggest that the continuous administration of metoclopramide is a useful option for belching insufficiency associated with cancer-related gastrointestinal obstruction. In the presence of gastrointestinal obstruction,gas retained in the stomach may be elevated/regurgitated through the peristalsis-promoting actions of metoclopramide,promoting belching.

Tapentadol was developed from tramadol by reducing its inhibitory effects on serotonin reuptake. In the present study, tapentadol was administered to a 49-year-old female esophageal cancer patient receiving a selective serotonin reuptake inhibitor (SSRI). On the day of administration, akathisia, nausea, dizziness, and insomnia developed. On the following day, she was diagnosed with serotonin syndrome, accompanied by fever, perspiration, myoclonic jerks mainly affecting the upper limbs, tremor of the extremities, and tachycardia. The diagnosis was made using three criteria. The symptoms disappeared immediately after discontinuation of tapentadol administration and initiation of benzodiazepine treatment. In Japan, tapentadol is an opioid analgesic for cancer pain management. If it is combined with an antidepressant, follow-up care is needed in consideration of serotonin syndrome.

Fentanyl buccal tablets place the tablet at the buccal site (above a rear molar, between the upper cheek and gum) and wait until it dissolves, but some patients may not be able to retain it due to defects of the maxillary molars. The aim of this study was to evaluate the effectiveness and safety of fentanyl buccal tablets when they were used outside the buccal site. Seven patients were treated with fentanyl buccal tablets outside the buccal site. For each of 5 episodes in which effective dose was identified, were investigated to average pain intensity assessed on a 0 to 10 numerical rating scale at 30 min postadministration and reduction in pain intensity of more than 33%. Pain intensity significantly decreased at 30 min postadministration in 5 patients with effective doses identified (p<0.001). In 92.0% of episodes treated, there was a reduction in pain intensity of more than 33%. Adverse events were somnolence and nausea with mild. However, these effects did not result in discontinuation of medication. Our findings suggested that fentanyl buccal tablets can be used effectively and safely even when patients used outside the buccal site.

The guide to proper use of methadone in Japan describes the SAG method (a method of stopping all leading opioids and starting methadone). Based on strict evaluation, our palliative care department introduces methadone by adding to the preceding opioid, and then tapering or discontinuation the preceding opioid. This time, we considered the clinical significance of 28 patients who received this method. In 20 of 28 cases (71.4%), methadone reached the maximum dose, and methadone titration could be safely performed without exacerbation of pain or serious adverse events. However, in order for this method to be performed safely, it is necessary to pay attention to the pharmacological properties of methadone, which has a long half-life, and to make a detailed evaluation and drug adjustment of the analgesic effect and adverse events after the introduction of methadone.