Context. Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.Objectives. We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.Methods. A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]eItem 5) $ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.Results. Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P ¼ 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P ¼ 0.048). Clinically meaningful pain improvement ($30%) was reported by 44.1% (n ¼ 15) of patients in Group D vs. 18.2% (n ¼ 6) in Group P (P ¼ 0.02); 32.4% (n ¼ 11) vs. 3.0% (n ¼ 1) of patients in Groups D and P, respectively, reported pain reduction $ 50% (P ¼ 0.002).Conclusion. Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine. J Pain Symptom

Background: Holistic multimodal interventions have not been established for cancer cachexia. The beliefs and perceptions of health care professionals (HCPs) based on their experiences influence the interventions. Objectives: HCPs' knowledge, perceptions, and practices in cancer cachexia management were evaluated. Design/Setting/Subjects/Measurements: A nationwide questionnaire survey was conducted that focused on the perspectives of HCPs on interventions in 451 designated cancer hospitals across Japan. Descriptive statistics were applied. Results: Among 2255 participants, 1320 responded (58.5%), and 1188 in 258 institutes were included in the analysis. The current international definition of cancer cachexia is not commonly known and recent clinical practice guidelines have not been widely adopted. More than 50% of participants considered ≥5% weight loss in six months and ECOG PS (Eastern Cooperative Oncology Group Performance Status) 2–4 to be cancer cachexia, whereas 50% answered that there was no relationship between life expectancy and cancer cachexia. Participants tended to consider it important to initiate nutritional and exercise interventions before cancer cachexia becomes apparent. The majority of participants recognized the importance of holistic multimodal interventions, particularly for the management of physical and psychological symptoms; however, only 20% reported that they educated patients and families. Furthermore, 33% of participants considered themselves to have provided patients and families with sufficient nutritional and exercise interventions and evidence-based information. Conclusion: The results reveal that HCPs are not regularly providing education and emotional support to patients and families suffering from cancer cachexia. The results also show the need for education for HCPs to enhance implementation of holistic multimodal interventions for cancer cachexia.

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ObjectiveThis post hoc, pooled, subgroup analysis of two randomised studies evaluated baseline characteristics that may influence the efficacy and safety of naldemedine in patients with opioid-induced constipation (OIC) and cancer.MethodsData for patients who received 0.2 mg naldemedine or placebo were pooled from randomised, placebo-controlled, phase IIb and phase III studies. Proportions of spontaneous bowel movement (SBM) responders and patients with diarrhoea were assessed for each treatment group. For the patient subgroups with or without possible blood–brain barrier (BBB) disruptions, changes in Numerical Rating Scale (NRS) and Clinical Opioid Withdrawal Scale (COWS) scores were assessed.ResultsA total of 307 patients were included in this analysis (naldemedine: n=155; placebo: n=152). The pooled proportion of SBM responders was 73.5% with naldemedine versus 35.5% with placebo. There was a significant increase in the proportion of SBM responders with naldemedine versus placebo (38.0% (95% CI 27.6% to 48.4%); p<0.0001). Greater proportions of SBM responders and patients who experienced diarrhoea were observed with naldemedine versus placebo in all subgroups. Changes from baseline in NRS and COWS scores were similar with naldemedine or placebo in patients with or without brain metastases.ConclusionsAlthough not powered to detect statistically significant differences in treatment effect among subgroups, this study demonstrated that naldemedine appeared to benefit patients with OIC and cancer, irrespective of baseline characteristics, and did not seem to affect analgesia or withdrawal–even in patients with potential BBB disruptions. Baseline characteristics did not appear to affect the incidence of diarrhoea in patients who received naldemedine.Trial registration numbersJapicCTI-111510 and JapicCTI-132340.

Objective: A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer. Patients and Methods: Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m² b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m², depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD. Results: The MTD of paclitaxel was presumed to be 60 mg/m², because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m². Therefore, the RD of paclitaxel was estimated to be 50 mg/m². The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m². Conclusion: Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m². This regimen could represent a novel and low toxic combination for advanced gastric cancer.