Comparison of primary endpoints between publications, registries, and protocols of phase III cancer clinical trials.

BACKGROUND: Decisions by leading journals to require trial registration and to make protocols of phase III randomized clinical trials (RCTs) publicly accessible were landmark events in clinical trial reporting. MATERIALS AND METHODS: We identified phase III cancer RCTs published between 2013 and 2015 in New England Journal of Medicine (NEJM), The Lancet, The lancet Oncology, JAMA and Journal of Clinical Oncology (JCO). RESULTS: We identified 345 reports of phase III RCTs of which 217 (62.9%) had available protocols. The availability rates for NEJM, The Lancet, The Lancet Oncology, JAMA and JCO were 98.0%, 33.3%, 22.7%, 55.6% and 88.3%, respectively. Journal and publication year were significantly associated with protocol availability. Eight of 215 trials (3.7%) with English language protocols had a discrepancy in primary endpoints between publication and protocol. Discrepancies of primary endpoints between protocol and registration existed in 16 (7.7%) of 209 trials. CONCLUSIONS: The policy of providing protocols with articles reporting RCTs has not been enforced rigorously. Selective reporting of primary endpoints only remains in a small fraction of phase III trials. Further improvement in consistency between primary endpoints registered and that in protocol is necessary.

Risk of second primary cancers in cancer patients treated with cisplatin: a systematic review and meta-analysis of randomized studies.

BACKGROUND: Case reports, retrospective analyses, and observational studies have linked the use of cisplatin to increased risk of second cancers, especially life-threatening secondary leukemia. We therefore performed a systematic review and meta-analysis to evaluate the risk of second cancers associated with receipt of cisplatin-based chemotherapy in randomized controlled trials (RCTs). METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing cisplatin- versus non-cisplatin-containing chemotherapy with data on second cancers. We extracted data about study characteristics and second cancers, especially leukemia/ myelodysplasia. The primary and secondary outcomes were the odds ratios (ORs) for all second cancers and for secondary leukemia/ myelodysplasia, respectively. RESULTS: We identified 28 eligible trials with 7403 patients. Second cancers were reported in 143 patients, including 75 patients in the cisplatin arm and 68 in the non-cisplatin arm (raw event rates of 1.91 and 1.96%, respectively). The pooled OR for risk of all second cancers associated with cisplatin-based chemotherapy was 0.95 (95% confidence interval (CI): 0.67-1.33, P = 0.76). Secondary leukemia/ myelodysplasia was reported in 14 patients on cisplatin arms and in 6 patients on non-cisplatin arms of 11 eligible RCTs with 2629 patients (raw event rates of 1.09 and 0.45%, respectively; pooled OR = 2.34, 95%CI 0.97-5.65, P = 0.06). CONCLUSION: Cisplatin was not associated with a significantly increased risk of second cancers compared with non-cisplatin-based chemotherapy. There is a non-significant trend to increased risk of leukemia/ myelodysplasia and the absolute risk was low. The concern about risk of second cancers should not influence decisions to use an efficacious regimen containing cisplatin.

Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) as second-line therapy for patients with advanced urothelial cancer.

There is currently no standard treatment for metastatic urothelial cancer after failure of cisplatin-based therapy. The present retrospective study investigated the efficacy and safety of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOX) in locally advanced or metastatic urothelial cancer patients following cisplatin-based treatment. Thirty-three patients who had received one or two cisplatin-based regimens were treated with oxaliplatin (85 mg/m2) as a 2-h infusion on day 1, LV (200 mg/m2) as a 2-h infusion followed by bolus 5-FU (400 mg/m2) on day 1, or a 44-h continuous 5-FU (1,200 mg/m2) infusion. Patients were a mean of 67 years old with two involved organs. Metastases were mostly in the lung (43%), lymph nodes (51%) and liver (46%). Based on an intention-to-treat analysis, nine patients achieved a partial response, with an overall response rate of 27%. Eight (24%) patients had stable disease. Mean progression-free survival was 3 months and mean overall survival was 6.1 months. Toxicity was mild to moderate with grade 3 or 4 neutropenia, thrombocytopenia and neuropathy occurring in 5 (15%), 4 (12%) and 2 (6%) patients, respectively. This study demonstrated that oxaliplatin plus 5-FU/LV was a well-tolerated second-line regimen with moderate activity in patients pretreated with cisplatin-based therapeutics.

Association of single-nucleotide polymorphisms rs2197076 and rs2241883 of FABP1 gene with polycystic ovary syndrome.

PURPOSE: The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS). METHODS: The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS. RESULTS: Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883. CONCLUSION: In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS.

Association of common variants of FTO in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and complex multisystemic genetic disease. Previous genome-wide association study (GWAS) of PCOS has found several potentially causative single nucleotide polymorphisms (SNPs) in Han Chinese population. The goal of present investigation was to assess the potential association between rs1121980, rs1421085, rs1558902, rs8050136 SNPs and PCOS. In order to make a better elucidation of this disease, further investigations of association between SNPs susceptibility and PCOS become necessary. METHODS: In the present study, we enrolled 212 patients with PCOS and 198 control subjects. Four polymorphisms of FTO gene (rs1121980, rs1421085, rs1558902, rs8050136) were genotyped by Taqman-MGB method, and their relationship with PCOS was speculated. RESULTS: The allele frequency has no significant difference between the PCOS group and the controls. Genotype frequencies of the four SNPs in the additive, dominant and recessive models showed no significant difference between PCOS cases and controls. CONCLUSIONS: Our results demonstrate that FTO gene has little association in PCOS development.

Species and distribution of rare earth elements in the Baotou section of the Yellow River in China.

This paper analyses the contents and species distributions of rare earth elements (REEs) in the water-suspended particulate-sediment system of the Baotou section of the Yellow River, China, with known anthropogenic REE input from industrial discharges. The major forms of REEs were suspended and dissolved in the mainstream and the tributaries of the Baotou section, respectively. The concentrations of the dissolved and suspended REEs had the same trends in the overlying water along the mainstream, which increased from the Seqi section (site A) to the mouth of the Sidaosha River (site D), reaching a maximum value at site D, and tending to decrease thereafter. The contents of REEs in sediment cores showed enrichment with light rare earth elements (LREEs). The bound to carbonates and to Fe-Mn oxides are the major forms of REE in the secondary phase and the REE exhibited LREE enrichment pattern and moderate Eu depletion in suspended particulates and surface sediments. The contents and species distributions of REEs in the water-suspended particulate-sediment system of the Baotou section suggest that the anthropogenic source of REEs from Baotou city have enhanced REE accumulation to the Baotou section. This information is important for predicting possible pollution resulting from anthropogenic REE input into rivers.

[Heavy metal adsorption research on different size fractions of sediment in the Baotou section of the Yellow River by using modified fractal dimension model].

The expression of surface fractal dimension (SFD) for size fractions of the Yellow River sediment was deduced. Based on the expression, the SFD value of different size fractions of the sediment was calculated. The SFD value of the sediment in the Baotou section of the Yellow River is 1.91, and the SFD value of the sediment smaller than 63 microm is 1.36, indicating strong ablation and separating ability of the Yellow River water. Using the modified fractal model, Freundlich model and Langmuir model to fit the data of heavy metal (Cu, Pb, Zn and Cd) adsorption, it is found that the modified fractal model is more available. And the adsorptive thermodynamics is better described by combining the modified fractal model and metastable equilibrium adsorption (MEA) theory. The variation extents of equilibrium adsorption capacity influenced by different grain size are ranked as Cu > Pb > Zn approximately equal to Cd. For each selected heavy metal, the higher initial concentration is, the stronger variation of adsorption capacity will be. The adsorptions of Cu and Pb are mainly associated with mineral composition of the sediment, while the adsorptions of Zn and Cd are mainly associated with physical characteristics of the sediment surface.

[Distribution characteristics of organic matter and total nitrogen in sediments of lake Wuliangsuhai].

Lake Wuliangsuhai is one of the representative inland freshwater lakes in grassland areas of China, and its shrinking and eutrophication is becoming more serious. The study on the ecological and environmental effects of the shrinking and eutrophication revealed that the total nitrogen (TN) content in the surface sediment of the lake had an obvious differentiation both in longitudinal and in latitudinal direction, and had a significant correlation with organic matter content. The mean C/N ratio of the sediment ranged from 12.07 to 19.95, which meant that the organic matter was mainly come from the hydrophytes of the lake, and the eutrophication of the lake was mostly caused by its internal load. Both TN and organic matter had a clear grain-size effect in different fractions of grain sizes of surface sediment, and their contents in IV (< 63 microm) were as 3.1 - 7.6 and 2.5 - 8.0 times as those in I (>250 microm), respectively.