Anlotinib or platinum-pemetrexed as second-line therapy in EGFR T790M-negative lung cancer.

BACKGROUND: Clinical management of T790M-negative patients after first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment failure is controversial. Anlotinib is a novel multi-target TKI for tumor angiogenesis and tumor cell proliferation, and it has been approved as a thirdline or beyond treatment for advanced non-small cell lung cancer (NSCLC). The impact of anlotinib as a second-line therapy compared with platinum-pemetrexed chemotherapy in T790M-negative patients after first-line EGFR-TKIs failed remains unclear. METHODS: In this retrospective cohort study, we reviewed 20 patients who were given anlotinib and 42 patients who received platinum-pemetrexed chemotherapy as a control after first-line EGFR-TKIs therapy progression. All the patients were confirmed to be T790M-negative using the cobas EGFR Mutation Test. The primary end point included progression-free survival (PFS) time, objective response rate (ORR) and disease control rate. RESULTS: The duration of PFS was significantly longer in the platinum-pemetrexed group than in the anlotinib group (median, 4.5 vs. 3.0 months; HR, 1.972; 95% CI, 1.078 to 3.607; P=0.021). The response rate was significantly better in the platinum-pemetrexed group (30.9%) than that in the anlotinib group (15%), and disease control rate (DCR) of both groups was 70% and 83%, respectively. All the adverse events in anlotinib group appeared to be manageable. CONCLUSIONS: Anlotinib was less effective than platinum-pemetrexed chemotherapy in T790M-negative NSCLC patients after disease progression with first-line EGFR-TKIs therapy failure.

[Association of C602A and T1559C polymorphisms of E-selectin gene and essential hypertension].

OBJECTIVE: To investigate the possible genetic associations between the C602A and T1559C polymorphisms of E-selectin (SELE) and essential hypertension. METHODS: Essential hypertensive patients (n = 500) and healthy normotensive subjects (n = 930) were screened for the genotypes C602A and T1559C by real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the SELE gene. RESULTS: Normotensive subjects and hypertensive patients were significantly different with respect to the genotypes CC, CA and AA, 26 (5.2%), 20 (4.0%) and 454 (90.8%) vs 14 (1.5%), 53 (5.7%) and 863 (92.8%) respectively of C602A. And the C-allele frequency was also significantly different between the NT and EH groups (C, A = 7.2%, 92.8% vs 4.4%, 95.6%). When subgrouped by gender, frequency of CC, CA, AA between normotensive and essential hypertensive males was 14 (4.7%), 11 (3.7%), 272 (91.6%) and 10 (1.7%), 34 (5.8%), 545 (92.5%), which differed significantly (P < 0.05), while in female groups, all the frequency of genotypes were significantly different (P < 0.01) except CC + CA. The additive model (TT, TC, CC) of the T1559C genotype was significantly different between essential hypertensive and normotensive groups overall, 57 (11.4%), 200 (40.0%), 43 (48.6%) and 66 (7.1%), 354 (38.1%), 510 (54.8%), respectively. The T-allele of hypertensive patients significantly differed from normotensive subjects (T, C = 31.4%, 68.6% vs 26.1%, 73.9% respectively). When subgrouped by gender, between the male NT and EH groups, the TT, TC and CC frequency of T1559C were 36 (5.9%), 117 (39.4%), 144 (48.5%) and 35 (5.9%), 230 (39.0%), 354 (55.0%), and the frequency of T vs C was 31.4% vs 68.6% and 26.1% vs 73.9%, which were significantly different (all P < 0.01). As in female NT and EH groups, there were not significant differences existed at all. CONCLUSION: C602A and T1559C of SELE are associated with essential hypertension in the Chinese population, and T1559C is closely related with male hypertension other than in females.

[Relationship between genetic polymorphisms of ß2-adrenergic receptor gene and essential hypertension risk among the Han Chinese population: a Meta analysis].

OBJECTIVE: To evaluate the relationship between A46G and C79G polymorphisms in the ß2-adrenergic receptor (ADRB2) gene and the incidence of essential hypertension (EH) among the Han Chinese population. METHODS: We conducted a computer retrieval of PUBMED, EMBASE, CNKI, Wanfang and VIP databases prior to May 2010. Articles investigating the relationship of EH and ADRB2 gene polymorphism of Han group were found through literature search, including 15 articles on A46G and 10 articles on C79G. According to the including and excluding criteria, a Meta-analysis was conducted in EH and ADRB2 gene polymorphism of A46G and C79G. The association was examined by RevMan4.2 software through quantitative analysis. RESULTS: Eight articles on A46G polymorphism (including 1078 EH cases and 788 control subjects) and six articles on C79G polymorphism (including 1367 EH cases and 1006 control subjects) were included in the current study. Meta-analysis showed that there was a significant association between A46G polymorphism and EH: genotype GG/(AA + AG) (fixed-effected model, OR = 1.35, 95%CI = 1.04 - 1.74, P = 0.02), genotype GG/AA (fixed-effected model, OR = 1.41, 95%CI = 1.06 - 1.89, P = 0.02). No significant association was found between C79G polymorphism and EH of Han group in China: G/C allele comparison (random-effected model, OR = 0.88, 95%CI = 0.55 - 1.39, P = 0.57). CONCLUSION: Significant association was found between A46G polymorphism of ADRB2 gene and EH, whereas no association could be found between C79G polymorphism and EH among Han Chinese population.