Comparison of kidney and hepatic outcomes among sodium-glucose cotransporter-2 inhibitors: a retrospective study using multiple propensity scores.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status. METHODS: Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values. RESULTS: Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively. CONCLUSIONS: Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status.

MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. OBJECTIVE: To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. METHODS: Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. RESULTS: There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC < median, n= 10), former group showed a significant improvement in the median progression-free survival compared with latter group (636 vs. 196 days, p = 0.032). CONCLUSIONS: MMP-9/ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

[The efficacy of aprepitant and palonosetron on cisplatin doublet in lung cancer].

Nausea and vomiting are major adverse reactions in cancer chemotherapy, and affect quality of life (QOL). We performed a retrospective study that examined the efficacy of aprepitant and palonosetron for chemotherapy-induced nausea and vomiting (CINV) on patients taking cisplatin doublets for lung cancer. The study subjects were 73 patients. A 5-HT(3) group received old-generation 5-HT(3) receptor antagonists and dexamethasone for preventive treatment (32 patients). An A group received old-generation 5-HT(3) receptor antagonists, aprepitant and dexamethasone (22 patients). An A+P group received palonosetron, aprepitant and dexamethasone (19 patients). On acute emesis (occurring within 24 hours after chemotherapy), there was no significant difference in the complete suppression rate of nausea and vomiting among the three groups. However, on delayed onset emesis (occurring between 24 to 120 hours), the complete suppression rate of nausea was significantly higher in the A+P group (57. 9%) than in the 5- HT(3) group (16. 7%) and A group (23. 8%). Significantly better efficacy was seen in the 5-HT(3) group and A group in the complete suppression rate of vomiting, and in the need of rescue medication rates on delayed-onset emesis. The cost of antiemesis was 19, 735 yen for the 5-HT(3) group, 32, 252 yen for the A group and 15, 557 yen for the A+P group. In conclusion, it was suggested that concurrent administration of palonosetron, aprepitant and dexamethasone for CINV on cisplatin doublet in lung cancer is a clinically useful treatment that might reduce the economic burden on patients.