Efficacy of Metformin in Patients With Breast Cancer Receiving Chemotherapy or Endocrine Therapy: Systematic Review and Meta-analysis.

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.

Effects of Proton Pump Inhibitors on Survival Outcomes in Patients with Metastatic or Unresectable Urothelial Carcinoma Treated with Pembrolizumab.

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.

Weight Loss Associated with Platinum-Based Chemotherapy in Patients with Advanced Lung Cancer.

BACKGROUND: We examined whether the weight loss that occurs with platinum-based chemotherapy in lung cancer patients is associated with chemotherapy side effects, treatment completion rates and therapeutic effect. METHODS: We retrospectively reviewed charts of advanced lung cancer patients treated with ≥2 cycles of platinum-based chemotherapy. Patients were divided into 2 groups based on ≥5 or <5% weight loss. Relationships between weight loss and other variables were investigated. RESULTS: Among 114 patients, 18 (15.8%) experienced ≥5% weight loss. Significantly more patients with small-cell lung cancer (SCLC) than with non-SCLC were found to have ≥5% weight loss (30.8 vs. 11.4%, p = 0.023). Patients with ≥5% weight loss experienced higher incidences of grade 3-4 leukopenia (p = 0.008) and neutropenia (p = 0.005), and treatment completion rates were lower in this group (p = 0.035). Weight loss was not significantly associated with therapeutic effect. CONCLUSION: The weight loss in patients with advanced lung cancer receiving platinum-based chemotherapy is associated with SCLC, grade 3-4 leukopenia, neutropenia and a decrease in treatment completion rate.

Risk factors for cytarabine-induced cutaneous toxicity in patients with haematological malignancies.

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.

[Effect of the administration of zoledronic acid on life expectancy in patients with multiple myeloma with or without renal impairment].

Zoledronic acid(ZA)is believed to exert anticancer effects in patients with multiple myeloma(MM). For patients with impaired renal function, its dosage should be determined according to creatinine clearance(Ccr). However, there is no reported difference in life expectancy improvement between those with and without renal impairment. Therefore, we conducted a retrospective study to investigate this clinical question. Seventy-eight MM patients receiving ZA injections were selected and divided into 2 groups: (1)normal group(n=39), baseline Ccr≥60mL/min, and(2)impaired group(n=39), baseline Ccr<60mL/min. Patients in the normal group received a significantly higher initial dose(p<0.001), were of a younger age(p<0.001), had lower b2-microglobulin(b2-M)levels(p<0.001), and had higher rates of prior hematopoietic stem cell transplantation(p<0.001)than those in the impaired group. We then compared the survival rate between 31 patients in the normal group and 27 patients in the impaired group whose treatment outcome data were available and found no significant difference(p=0.251). Therefore, our results suggest that the survival rate on ZA administration may not differ between MM patients with and without renal impairment.

Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study.

OBJECTIVE: It was reported that the administration of tramadol in patients with cancer pain who have a higher interleukin 6 (IL-6) serum level led to insufficient pain relief. Cytokines produced by tumors, including IL-6, are associated with cancer cachexia. However, whether nonresponse to tramadol is related to cancer cachexia is unknown. The purpose of this study was to examine the relationship between tramadol response and cancer cachexia in patients with cancer pain. METHODS: We conducted a retrospective cohort study of patients with cancer who received tramadol treatment for mild to moderate pain from January 2016 to June 2019. Patients who experienced <20% pain reduction based on the numeric rating scale from baseline to day 7 after treatment with tramadol were defined as nonresponders. Univariate and multivariate logistic regression analyses were conducted to examine the relationships between tramadol response and various patient characteristics, including cancer cachexia. RESULTS: Of 115 patients, 79 were included in the analysis. A total of 24 patients experienced cancer cachexia, and 22 patients were nonresponders. In the univariate logistic analysis, cancer cachexia (odds ratio [OR]: 6.04, 95% confidence interval [CI]: 2.06-17.7), higher white blood cell counts (× 103/µL; OR: 1.28, 95% CI: 1.04-1.61), and lower body mass index (OR: 0.79, 95% CI: 0.66-0.96) were significantly associated with nonresponse to tramadol. The multivariate logistic analysis revealed that cancer cachexia (OR: 5.27, 95% CI: 1.75-15.9) was the only significant factor associated with nonresponse to tramadol. CONCLUSIONS: Cancer cachexia in patients with cancer pain can be associated with nonresponse to tramadol.

Risk Factors for Polypharmacy in Elderly Patients With Cancer Pain.

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 [CI], 2.57-11.42, P < .001), poor PS (OR: 4.50, 95% CI, 1.06-31.68, P = .039), and administration of an anticancer or molecular targeted drug (OR: 2.78, 95% CI, 1.13-7.16, P = .025). CONCLUSIONS: An increased number of comorbidities, poor PS, and administration of an anticancer or molecular targeted drug were considered risk factors for PP in elderly patients with cancer pain. Sharing these risk factors with medical staff will help reduce the occurrence of problems associated with PP.