Background: The risk factors for cytarabine (Ara-C)-induced cutaneous toxicity are unclear. Methods: We retrospectively reviewed the medical charts of patients with haematopoietic malignancies treated with Ara-C and examined risk factors for Ara-C-induced cutaneous toxicity. Results: We reviewed 114 patients (76 men, 38 women) and found that 47 patients (41.2%) experienced cutaneous toxicity. In 93 patients (81.6%) with non-Hodgkin's lymphoma (NHL) and acute myeloid leukaemia (AML), the toxicity was significantly associated with the cancer type [AML/NHL: odds ratio (OR) = 4.84; 95% confidence interval (CI) = 1.99-11.81; p = 0.001], age (<50/≥50 years: OR = 2.54; 95% CI = 1.08-5.95; p = 0.032) and concurrent steroid administration (yes/no: OR = 0.22; 95% CI = 0.09-0.56; p = 0.001). AML was the only significant association (OR = 3.83; 95% CI = 1.21-12.06; p = 0.022) in the multivariate logistic analysis. Conclusion: AML, age <50 years and no steroid use are considered to be risk factors for Ara-C-induced cutaneous toxicity.

The gut microbiome influences tumor response to immune checkpoint inhibitors (ICIs). The proton pump inhibitors (PPI) significantly impair diversity of the gut microbiota and can affect the efficacy of ICIs. Therefore, the present study aimed to evaluate the influence of PPI on survival in patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. We conducted a retrospective cohort study of patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. The use of PPI was defined as any administration for ≥30 d within 60 d prior and/or 30 d after treatment initiation. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and Cox proportional hazards regression analysis was performed to investigate prognostic factors based on patient characteristics. Seventy-nine patients were included in the analysis, and 34 patients (43.0%) received PPI. There were no significant differences in OS and PFS between PPI users and nonusers (median OS: 8.2 months vs. 11.2 months, hazard ratio (HR): 1.36, 95% confidence interval (CI): 0.75-2.42, p 0.296; median PFS: 3.5 months vs. 5.1 months, HR: 1.63, 95% CI: 0.95-2.80, p 0.069). In the multivariable analysis, PPI use was not associated with OS (HR 0.80, 95% CI 0.40-1.56, p 0.526) or PFS (HR 1.44, 95% CI 0.79-2.60, p 0.233). In conclusion, the estimated effect size of PPI use on survival in Japanese patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab was not reproducible.

Background Previous studies have suggested that metformin might improve survival outcomes in patients with breast cancer. However, findings on the efficacy of metformin with chemotherapy or endocrine therapy are inconsistent. Objective To clarify the efficacy of metformin with chemotherapy or endocrine therapy in breast cancer patients according to the treatment setting, including neoadjuvant, adjuvant, and metastasis/recurrence. Methods We systematically searched for randomized controlled trials (RCTs) in MEDLINE, CENTRAL, and EMBASE from inception through July 2020. Overall survival (OS), progression-free survival (PFS), and hypoglycemia rate were the primary outcomes. Secondary outcomes included severe adverse events (SAEs) and relapse-free survival. We used the Grading of Recommendations Assessment, Development, and Evaluation approach and performed a meta-analysis to evaluate the efficacy and safety of metformin with chemotherapy and endocrine therapy in patients with breast cancer. Results Our systematic review included 412 participants from 5 trials. Metformin showed little to no difference in OS (hazard ratio [HR] = 1.13; 95% CI = 0.71-1.81; certainty of evidence [COE], moderate) and PFS (HR = 1.14; 95% CI = 0.86-1.50; COE, moderate) in patients with metastasis/recurrence. The evidence was very uncertain about the effect of metformin on survival outcomes in patients who received metformin with neoadjuvant or adjuvant treatment. Metformin showed little to no difference in hypoglycemia and SAEs. Conclusion and Relevance Metformin should be discouraged routinely in nondiabetic patients with metastatic/recurrent breast cancer. Further RCTs are needed to verify whether metformin with chemotherapy or endocrine therapy results in significant clinical benefits in the neoadjuvant or adjuvant setting.

Dacarbazine (DTIC) produces adverse reactions including local venous pain during the intravenous injection. DTIC is reported to be photolyzed to produce certain kinds of pain producing substances. 5-diazoimidazole-4-carboxamide (Diazo-IC) is considered to be a causative photolyte of venous pain. A newly designed cover shield has been used at Osaka University Hospital when DTIC is administered for the last 4 years. This shield comprises black cotton and covers both the infusion bag and route of infusion. We evaluated the effectiveness of this new shield against photodegradation of DTIC by determining the concentration of Diazo-IC. DTIC was dissolved with an injection solvent and mixed with 5％ dextrose in water. Prepared samples were divided into 3 groups (without shield, infusion bag covered with shield, and infusion bag and infusion route covered with shield) and exposed under natural light conditions indoors. Prepared solutions ran down through the route and those samples were taken before and after passing the route pipe. Diazo-IC in the samples was measured by HPLC. Production of Diazo-IC in the non-covered bag was significantly increased in comparison with that in covered infusion bags. Diazo-IC production in samples after passing through the route was significantly increased compared with that in samples taken before passing through the route of the non-covered shield and covered infusion bag only. For the covered infusion bag and infusion route, the samples taken before and after passing through the route did not show significant differences. These data suggest that the new shield, which almost perfectly covers both the infusion bag and route of infusion, is effective in preventing DTIC photodegradation.

Objective: Polypharmacy (PP) is a burden in elderly patients with cancer pain; however, risk factors for PP remain unclear. The purpose of this study was to investigate the risk factors for PP in this patient population. Methods: We retrospectively reviewed the medical charts of patients aged 65 years with cancer pain who were treated at Osaka University Hospital between February 2014 and June 2016 according to the World Health Organization 3-step ladder for cancer pain relief. We defined PP as 5 medications and conducted exploratory research to examine the association between PP and patient characteristics. Performance status (PS) was estimated according to the Eastern Cooperative Oncology Group system and is categorized as good PS (0-1) and poor PS (2-4). Results: We reviewed 206 patients (122 men and 84 women) with a median age of 71 years (range, 65-89 years) and found that 174 patients (84.5%) had PP. In multivariate logistic analysis, PP was significantly associated with an increased number of comorbidities (odds ratio [OR]: 4.93, 95% confidence interval [