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C.P. Hu



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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-024 - Evaluation of Vascular Normalization in Human Lung Adenocarcinoma Induced by EGCG and the Efficacy of Combine Chemotherapy in Its Normalization Time Window (ID 1917)

      14:52 - 15:06  |  Author(s): C.P. Hu

      • Abstract

      Background
      Microvasculature and microenvironment play important roles in proliferation, metastasis and prognosis in human lung adenocarcinoma, which might be altered by many anti-angiogenic drugs and cause “vessel normalization”. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors. So we hypothesizing that EGCG might cause “vessel normalization”, and in addition combined chemotherapy exert a synergistic effect in the tumor vessel normalization window caused by EGCG.

      Methods
      Build nude mice xenograft tumor model(A549 cell line). Randomly divided them into three groups (treated with saline, EGCG, bevacizumab). Test following indexes at day of 0, 2, 4, 6, 9, 12: Vessel structure: MVD, MPI; vessel GBM; Transmission-electron-microscope of microvessles; Vessel functional: perfusion function, vessel permeability; Microenvironment effect: IFP, PO2. Test cisplatin concentration in tumor tissues with different combination of EGCG and cisplatin. Treated mice with saline, cisplatin, EGCG, EGCG+cisplatin on day0 and EGCG+cisplatin on day5 and record growth delay.

      Results
      EGCG treated group undergoing a persisting decrease of MVD, a gradual decrease of MPI, a transient elevation of vessel perfusion function, permeability and PO2, transient decrease of IFP in tumor tissue. Full-dose cisplatin at day5 had a concentration significantly higher than Full-dose at day0 and half-dose at d5. Statistical analysis shows EGCG and cisplatin had synergistic effect as a combined anti-tumor chemotherapy. Combined treatment groups had significantly lower xenograft tumor growth rates than other three groups, and tumor growth rate in combining cisplatin on day5 was significantly lower than on day0.

      Conclusion
      EGCG causes vessel normalization in human lung adenocarcinoma tumor, the window is between Day 4 to Day 9. Combined therapy in this window period can escalate drug concentration in local tumor tissue, and leads to anti-tumor synergistic effect, providing a new strategy for EGCG applying as a complementary chemotherapy drug.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-048 - Real-world evidence for clinical effectiveness, toxicity, and hospitalization costs associated with second-line chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (ID 3101)

      09:30 - 09:30  |  Author(s): C.P. Hu

      • Abstract

      Background
      Real world evidence for clinical effectiveness, toxicity, and hospitalization costs associated with second-line chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) is needed to guide clinical practice and reimbursement decision making in China.

      Methods
      This study retrospectively identified advanced non-squamous NSCLC patients treated with second-line chemotherapy between 2007 and 2012 in four triple-A hospitals. Patients’ baseline characteristics, chemotherapy, clinical response, adverse events, and hospitalization costs were extracted from medical and financial records associated with hospitalizations during second-line chemotherapy. They were compared by treatment using descriptive statistical methods. Kaplan-Meier (KM) survival analysis was conducted to explore the differences in time to progression (TTP) between the treatments. Hospitalization costs were stratified into non-drug costs and non-chemotherapy drug costs, and chemotherapy drug costs. Propensity score methods were used to create matched patients with balanced baseline characteristics to confirm the findings in the unadjusted analyses.

      Results
      414 patients received pemetrexed singlet (n=57), docetaxel singlet (n=64), docetaxel-platinum doublet (n=119), and pemetrexed-platinum doublet (n=174) as second-line chemotherapy in the four hospitals. The identified patients had similar baseline characteristics except that patients receiving docetaxel-platinum doublet (53.2 years vs. 58.5 years, p = 0.003) or pemetrexed-platinum doublet (54.3 years vs. 58.5 years, p = 0.010) were younger than those treated by pemetrexed singlet. KM survival analysis indicated a non-significant trend suggesting longer mean TTP for pemetrexed singlet than that for docetaxel singlet (95.6 days vs. 53.4 days; p = 0.139), for docetaxel-platinum doublet (95.6 days vs. 52.4 days; p = 0.139), and for pemetrexed-platinum doublet (95.6 days vs. 76.3 days; p = 0.716). The adverse event comparisons demonstrated that pemetrexed singlet had lower incidence rates for neutropenia (8.8% vs. 25.0%, p = 0.035 for docetaxel singlet; 21.9%, p = 0.055 for docetaxel-platinum doublet; 23.0%, p = 0.031 for pemetrexed-platinum doublet) and leukopenia (10.5% vs. 21.9%, p = 0.152 for docetaxel singlet; 28.6%, p = 0.013 for docetaxel-platinum doublet; 26.4%, p = 0.021 for pemetrexed-platinum doublet) and had lower incidence rates for vomiting (35.1% vs. 62.6%, p < 0.001) and nausea (43.9% vs. 69.0%, p < 0.001) than pemetrexed-platinum doublet. Pemetrexed singlet was associated with the lowest hospitalization costs per treatment cycle (3 weeks) for non-drug expenses (RMB 3,949 vs. RMB 5,154 for docetaxel singlet, p = 0.043; RMB 6,067 for docetaxel-platinum doublet, p = 0.002; RMB 5,045 for pemetrexed-platinum doublet, p = 0.029; 1 RMB = 0.16 US$) and non-chemotherapy drugs (RMB 5,471 vs. RMB 8,421 for docetaxel singlet, p = 0.006; RMB 7,874 for docetaxel-platinum doublet, p = 0.015; RMB 7,665 for pemetrexed-platinum doublet, p = 0.009). Similar trends were observed in the comparisons between the treatments in propensity score matched patients.

      Conclusion
      Advanced non-squamous NSCLC patients treated with pemetrexed singlet for second-line therapy had less toxicity and lower hospitalization costs for non-drug expenses and non-chemotherapy drugs in this Chinese cohort. When compared to pemetrexed singlet, pemetrexed-platinum doublet as second-line chemotherapy was associated with greater occurrence of adverse events and higher hospitalization costs without giving any additional survival benefits.

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    P2.01 - Poster Session 2 - Cancer Biology (ID 145)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.01-022 - Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2 (ID 1939)

      09:30 - 09:30  |  Author(s): C.P. Hu

      • Abstract

      Background
      Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined.

      Methods
      Build nude mice xenograft tumor model(A549 cell line). Treat them with EGCG(i.p.), Counting MVD labeled by CD31, observing Ang-1 and Ang-2 expressions detected by quantum dots double-label immunofluorescence assessment. interstitial fluid pressure (IFP) was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were performed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent.

      Results
      EGCG treatment led to a significant decrease of MVD, and of Ang-2 expression, while Ang-1 decreased with no significance. Both IFP and hypoxia were decreased. Tumor growth studies show that EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R2 = 0.618, P = 0.002), Ang-2 was correlated with MVD (R2 = 0.423, P = 0.022), IFP (R2 = 0.663, P = 0.01) and PIMO staining (R2 = 0.694, P = 0.01).

      Conclusion
      IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.