The lesion site in malignant psoas syndrome influences the cancer pain intensity.

BACKGROUND: Malignant psoas syndrome (MPS) is characterized by pain and hip flexion fixation due to tumor infiltration of the iliopsoas muscle. However, the dose of opioid required to control pain varies markedly among MPS patients. As the ability to predict whether an MPS patient will need a higher opioid dose in the early period of pain control is clinically meaningful, we retrospectively evaluated the relationship between lesion site in MPS and the opioid dose required for pain control. METHODS: Fourteen patients received opioid control of cancer pain due to MPS between January 2014 and December 2018. Two patients with paraplegia who died during pain control were excluded from this study. The remaining 12 patients were divided into group of muscle attachment (group MA) (n=6), with the lesion in the iliopsoas MA to the spine, and group of muscle belly (group MB) (n=6), with the lesion in the iliopsoas MB. We compared opioid doses for pain control between groups. RESULTS: No significant differences in background characteristics were seen between groups. Opioid dose (in oral morphine equivalents) was significantly higher in group MB (1,374.3±504.5 mg/day) than in group MA (92±67.9 mg/day; P=0.0007). CONCLUSIONS: MPS patients with the lesion in the MB appear to need a higher opioid dose for pain control than patients with the lesion in the MA.

Analysis of Predictive Factors for Diarrhea after the Administration of Naldemedine.

Naldemedine (NAL), a peripherally acting µ-opioid receptor antagonist, is effective for opioid-induced constipation (OIC). However, diarrhea is the most common adverse event. We investigated the incidence of NAL-induced diarrhea in patients who started NAL at Nagasaki University Hospital between June 2017 and March 2019. Predictors of NAL-induced diarrhea were analyzed using a multivariate logistic regression model. Two hundred and forty-two patients were included in the present study, and NAL-induced diarrhea was observed in 17.8% (43 patients). The results of multiple logistic regression analyses identified the administration of opioid analgesics for 8 d or longer before the initiation of NAL (odds ratio (OR): 2.20, 95% confidence interval (95% CI): 1.04-4.64, p = 0.039), the combination of a laxative (OR: 2.22, 95%CI: 1.03-4.81, p = 0.042), and the combination of CYP3A4 inhibitors (strong/moderate) (OR: 2.80, 95%CI: 1.02-7.67, p = 0.045) as risk factors. Therefore, the development of diarrhea needs to be considered in patients with these risk factors. Furthermore, diarrhea may be controlled by the initiation of NAL within 7 d of opioid analgesics and, where possible, the discontinuation of or change in the combination of moderate or strong CYP3A4 inhibitors.

Naldemedine-induced Opioid Withdrawal Syndrome in a Patient with Breast Cancer without Brain Metastasis.

Opioid-induced-constipation (OIC) can be treated by naldemedine and other peripherally acting mu-opioid receptor antagonists (PAMORA) via a novel mechanism. We describe the case of a 52-year-old female outpatient who developed OIC while receiving oxycodone for pain due to cancer with multiple bone metastases. Although she did not have brain metastasis, opioid withdrawal syndrome (OWS) developed after taking naldemedine orally. Her Clinical Opiate-Withdrawal Score (COWS) was 19 (moderate symptoms). However, she recovered from OWS on intravenous fentanyl and a continuous infusion of oxycodone. She did not develop OWS thereafter and was discharged two days after recovery.

Combination index of the concentration and in vivo antagonism activity of racemic warfarin and its metabolites to assess individual drug responses.

The present study was undertaken to examine whether in vivo vitamin K epoxide reductase complex 1 (VKOR) "actual" antagonism activity, calculated by the concentrations and the reported anticoagulant activities of the R- and S-warfarin enantiomers and their metabolites, correlates with the weekly dose of warfarin. Five patients under palliative care were enrolled in our study and 20 serum samples were analyzed by an enantioselective high-performance liquid chromatography-ultraviolet detection method. In vivo VKOR inhibition activities of S-warfarin, R-warfarin, 7- and 10-hydroxywarfarin were calculated as the ratio of drug or metabolite concentration to the IC50. The mean drug concentrations (± SD) of S- and R-warfarin, 7-hydroxywarfarin and 10-hydroxywarfarin were 334 ± 154 ng/ml, 370 ± 115 ng/ml, 42 ± 15 ng/ml and 80 ± 44 ng/ml, respectively. Then, in vivo VKOR actual antagonism activities of S- and R-warfarin, 7-hydroxywarfarin and 10-hydroxywarfarin were calculated. Good correlation (R2 = 0.69-0.72) was obtained between the weekly warfarin dose and the ratios of INR/actual antagonism activity, while poor correlation was observed between the weekly warfarin dose and INR (R2 = 0.32) or the activities (R2 = 0.17-0.21). Actual antagonism activities along with the INR correlated well with the warfarin dose. This parameter may be useful for predicting or altering warfarin doses, although further verification in a larger study is required.

Efficacy and Safety of Oxycodone Injection for Relieving Cancer Pain: A Study in Japan Consisting of Two Open Trials for Intravenous and Subcutaneous Administration.

Pure oxycodone injection became increasingly necessary after oral oxycodone was launched in Japan in 2003. However, trials clarifying the efficacy and safety of injection are rare. Therefore, a multicenter open study on injection was designed and carried out in 2010, resulting in the launch of injection therapy in 2012. As published domestic case reports on efficacy already show widespread prescription, this study aimed to provide useful information for cancer pain relief in Japan and other countries. Our oxycodone injection study consisted of two trials, one of intravenous (S#9131) and the other of subcutaneous (S#9132) administration. The minimum required number of enrolled patients suffering cancer pain was determined to be 70 in S#9131 and 20 in S#9132. These studies had the same dose-titration protocol as the main endpoint, i.e., pain relief rate (PRR) defined as the rate of achieving adequate pain control (APC), as in prior oral oxycodone trials in Japan. In S#9131, PRR was 81.4% (95% confidence interval: 70.3-89.7%), therefore, the null hypothesis of PRR<70% was rejected using the binominal one-sided test (p=0.0217). In S#9132, PRR was 73.7% also surpassing 70%. Safety was also assessed in the same way as in prior trials. The majority of adverse effects were moderate or mild and recovered with no sequelae. As shown above, the injection was considered to be effective and safe in cancer pain treatment. The details of these trials, particularly the dose-titration protocol for achieving APC and route switching information, are expected to enhance injection convenience for prescribers.