Impact of metformin use on survival outcomes in non-small cell lung cancer treated with platinum.

Preclinical evidence suggests that metformin, a widely used antidiabetic drug, may have a sensitizing effect on platinum. The purpose of this study was to evaluate the survival outcomes for non-small cell lung cancer (NSCLC) patients with type 2 diabetes mellitus (T2DM) using metformin during platinum-based chemotherapy.The clinicopathological parameters and survival data of 75 NSCLC patients with T2DM from January 2008 to December 2011 were collected and analyzed retrospectively. Patients were divided into 2 groups: metformin exposure group (n = 27) and non-metformin group (patients using other hypoglycemic agents or no drug for controlling n = 48). Univariate and multivariate analyses were performed to assess the association of metformin usage with overall survival (OS).Mean follow-up time was 58.7 months. The mean survival time was 36.74 months in the metformin group and 40.21 months in the non-metformin group. There was no significant difference in survival time between the 2 groups (P = .661). After adjusting gender, age, smoking status, tumor stage, tumor histology, and differentiation, multivariate analysis showed that metformin was not associated with the OS in NSCLC patients treated with concurrent platinum-based chemotherapy (hazard ratio: 1.071, 95% confidence interval: 0.577-1.986, P = .828).Our results indicated that metformin exposure had no significant effect on OS in NSCLC patients treated with platinum-based chemotherapy. Further studies are warranted to evaluate whether metformin could affect the survival of NSCLC patients treated with platinum-based chemotherapy.

In vitro interaction of deferiprone with cellular membrane transporters of hOCTs and hOAT1 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a LC-MS/MS method for determination of deferiprone in cell lysate and to study the potential interaction between deferiprone and hOCTs or hOAT1 transporters in vitro.</p><p><b>METHODS</b>The determination was performed on an Agilent Eclipse Plus C18 column(3.5 μm, 2.1 mm×50 mm).The gradient mobile phase was composed of solvent A:0.1% formic acid in water, and B:0.1% formic acid in acetonitrile. The mass spectrometer with an electrospray interface was operated in positive ion mode with multiple reaction monitoring (MRM) scan mode monitored the ion pair of deferiprone at m/z 140→96, or phenacetin at m/z 180→110. The effects of deferiprone on the accumulation of typical substrates of hOCTs and hOAT1 were evaluated by MDCK-hOCTs and MDCK-hOAT1 cells respectively. The accumulation of deferiprone was also investigated in MDCK-hOCTs cells and mock cells with or without typical inhibitors.</p><p><b>RESULTS</b>The standard curve was linear over the range of 5-300 nmol/L. The assay recovery of deferiprone was above 94%, and the intra-day precision (RSD) was less than 2.0%. The accumulation of MPP(+) in MDCK-hOCTs cells with 300 μmol/L deferiprone were 73.5%, 87.1% and 70.4%, respectively. The uptake of deferiprone in MDCK-hOCTs and mock cells did not show significant difference. Deferiprone of 100 μmol/L did not significantly affect the accumulation of 6-CF in MDCK-hOAT1 cell.</p><p><b>CONCLUSION</b>The method is sensitivity and suitable for the determination of deferiprone in cell lysate. Deferiprone can significantly inhibit hOCT1 and hOCT3, but has no effects on hOCT2 and hOAT1. hOCTs may not play a major role in the transport of deferiprone.</p>