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Pretreatment Red Blood Cell Total Folate Concentration Is Associated With Response to Pemetrexed in Stage IV Nonsquamous Non-Small-cell Lung Cancer.
Bagley, SJ, Vitale, S, Zhang, S, Aggarwal, C, Evans, TL, Alley, EW, Cohen, RB, Langer, CJ, Blair, IA, Vachani, A, et al
Clinical lung cancer. 2017;(2):e143-e149
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Abstract
INTRODUCTION Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Previous studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic, marker of cellular folate status was associated with the response to pemetrexed-based chemotherapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS We conducted a prospective cohort study of patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy containing pemetrexed. The pretreatment RBC total folate level was quantified using liquid chromatography mass spectrometry. We then compared the objective response rate (ORR) between patients with RBC total folate concentrations greater than and less than an optimal cutoff value determined from the receiver operating characteristic curve. A logistic regression model was used to adjust for age, sex, and the use of bevacizumab. RESULTS The ORR was 62% (32 of 52 patients). Receiver operating characteristic analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and nonresponders. Patients with RBC total folate < 364.5 nM had an ORR of 27% compared with 71% for patients with RBC total folate > 364.5 nM (P = .01). This difference persisted after adjusting for age, sex, and the use of bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01). CONCLUSION A low pretreatment RBC total folate was associated with an inferior response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response.
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Association between folate intake and risk of head and neck squamous cell carcinoma: An overall and dose-response PRISMA meta-analysis.
Fan, C, Yu, S, Zhang, S, Ding, X, Su, J, Cheng, Z
Medicine. 2017;(42):e8182
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Abstract
The results of published studies about the relationships between folate intake and risk of head and neck squamous cell carcinoma (HNSCC) remained inconsistent. Hence, a comprehensive and dose-response meta-analysis was performed to clarify the association between folate intake and HNSCC risk.The electric searches of Pubmed, Medline, and EMBASE databases were performed to identify the studies examining the relationship between folate intake and HNSCC risk on April 5, 2017. According to the inclusion criteria, finally 9 studies were included in this meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Dose-response analysis was conducted to quantitate the relationship between dietary folate intake and HNSCC risk.The pooled OR for assessing the risk of HNSCC and folate intake in the highest level versus lowest level was 0.505 (95% CI 0.387-0.623). The linearity model of dose-response analysis indicated that with increased 100 μg/d folate intake, the risk of HNSCC decreased 4.3% degree (OR 0.957, 95% CI 0.935-0.980).These results indicate that folate is a protective nutrient against HNSCC carcinogenesis.