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P1.03-036 Adjuvant Chemotherapy with Uracil-Tegafur for Pathological T1aN0M0 Lung Adenocarcinoma with Lymphatic Vessel Invasion
S1964 group and the anti-tumor effect of B1206 and cisplatin was comparable. However, combination of B1206 and cisplatin did not show significant difference in tumor size when compared with single drug treatment. Conclusion: This study suggests that B1206 could be used as a new concept of therapy for NSCLC by inhibiting the non-canonical function of LRS and that continuous efforts are required on exploring non-canonical function of ARS as well as its inherent function for protein synthesis. Keywords: Leucyl-tRNA synthetase (LRS), B1206, non-small cell lung cancer (NSCLC)
P1.03-035 Efficacy of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC J. Bosch Barrera,1 E. Sais,1 S. Verdura,2 E. Cuyas,2 D. Roa,1 A. Hernández,1 A. Izquierdo,1 E. Teixidor,1 W. Carbajal,1 M. Lopez,3 J. Brunet,1 J.A. Menendez4 1Catalan Institute of Oncology. Hospital Universitari Dr. Josep Trueta, Girona/ES, 2Girona Biomedical Research Institute (Idibgi), Molecular Oncology Group, Salt/ES, 3Pharmacy Department, Catalan Institute of Oncology. Hospital Universitari Dr. Josep Trueta, Girona/ES, 4Procure (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona/ES Background: Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1e3, PDGFa and b, and FGFR1e3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy. The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exert significant anti-cancer effects in pre-clinical models. The oral use of the silibinin-containing nutraceutical Legasil® could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment. Method: Patients with stage IV NSCLC who failed 1 prior treatment were eligible for nintedanib/docetaxel combination. We present data of patients that received nintedanib plus docetaxel with or without combination with up to 5 capsules/day of Legasil®, which equated to a 630 mg/ day dose silibinin regimen, as complementary treatment. The nature of the interaction between nintedanib and silibinin was explored in a broad panel of human NSCLC cell lines. Result: Twenty-two patients were enrolled in the study: median age 63y (range: 44e74); male: 14. All the cases were non-squamous NSCLC. All patients had received first line therapy; 3 patients had 2 prior lines of treatment. The mean PFS was 1.82 months (95% confidence interval [CI] 1.39e2.26) for the nintedanib plus docetaxel combination (n¼7) versus 4.97 (95%CI 2.87e7.07) for the nintedanib, docetaxel and Legasil® triple combination (n¼15) (p¼0.02). No statistically significant differences in mean OS were observed between the two arms: 4.88 (95%CI 3.26e6.48) for nintedanib plus docetaxel versus 10.3 (95%CI 5.85e14.76) for nintedanib plus docetaxel plus Legasil® (p¼0.534). At the data cutoff in June 2017, 9 (41%) patients remained alive. A significant inverse correlation was found between nintedanib and silibinin sensitivity among NSCLC cell lines. The combined treatment of nintedanib and silibinin produced unanticipated, synergistic cytotoxic effects in nintedanib-unresponsive NSCLC cells. Conclusion: There is a clinical and biological rationale for combining nintedanib and docetaxel with the silibinin-containing nutraceutical Legasil® in patients with advanced NSCLC, where few effective second-line treatment options are available. Keywords: silibinin, nintedanib, docetaxel
Journal of Thoracic Oncology
Vol. 12 No. 11S2
P1.03-036 Adjuvant Chemotherapy with Uracil-Tegafur for Pathological T1aN0M0 Lung Adenocarcinoma with Lymphatic Vessel Invasion Y. Kitamura, W. Nishio, H. Tanaka, K. Minami, H. Okuma, M. Yoshimura Chest Surgery, Hyogo Cancer Center, Akashi/JP Background: The aim of this retrospective study was to investigate the efficacy of adjuvant chemotherapy for patients in pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion. Method: We retrospectively collected data on 72 consecutive patients with pathological T1aN0M0 (the 7th edition of the UICC TNM stating system) lung adenocarcinoma with lymphatic or/and vessel invasion from January 2001 to December 2013. Adjuvant uracil-tegafur group were compared with control group. Overall survival (OS) and diseasefree survival (DFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Prognostic factors were evaluated using a Cox proportional hazard model. Result: Among the 72 patients, 21 patients (29.1%) were treated with adjuvant chemotherapy with uraciletegafur. No significant difference was found in patient characteristics between the two groups. In the 21 adjuvant chemotherapy and 51 control groups, the 5-year OS rates were 100% versus 80.8%, respectively; and the 5-year DFS rates were 88.2% versus 65.1% (p¼0.0138), respectively. Multivariate analysis revealed that adjuvant chemotherapy was only independent predictor of OS and DFS (p ¼ 0.014, 0.013, respectively). Conclusion: Adjuvant chemotherapy with uraciletegafur improves survival among patients with completely resected pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion. Our study suggests that pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion potentially benefits from adjuvant chemotherapy. Keywords: non-small cell lung cancer, adjuvant chemotherapy, Lymphatic vessel invasion
P1.03-037 A Phase II Study of Adjuvant Chemotherapy with Docetaxel plus Nedaplatin for Completely Resected Non-Small Cell Lung Cancer K. Teramoto,1 Y. Namura,2 K. Hayashi,2 K. Ishida,2 K. Ueda,2 K. Okamoto,2 R. Kaku,2 T. Hori,2 Y. Kawaguchi,2 T. Igarashi,2 M. Hashimoto,2 Y. Ohshio,2 S. Kitamura,2 M. Motoishi,3 Y. Suzumura,4 S. Sawai,3 J. Hanaoka,2 Y. Daigo1 1Department of Medical Oncology, Shiga University of Medical Science, Otsu/JP, 2 Department of Surgery, Shiga University of Medical Science, Otsu/JP, 3 Department of Thoracic Surgery, National Hospital Organization Kyoto Medical Center, Kyoto/JP, 4Department of Thoracic Surgery, Ijinkai Takeda General Hospital, Kyoto/JP Background: Nedaplatin, a cisplatin derivative, has similar activity to cisplatin for non-small-cell lung cancer (NSCLC). We previous reported that the combination chemotherapy of docetaxel plus nedaplatin was well tolerated in patients with advanced NSCLC. The purpose of this phase II study was to evaluate the feasibility of combination chemotherapy of docetaxel plus nedaplatin as adjuvant chemotherapy in patients with completely resected stage IB-IIIA NSCLC. Method: Following a radical surgery, patients were treated with docetaxel (60 mg/m2) and nedaplatin (80 mg/m2) on day 1 every four weeks up to four cycles. The primary endpoint was feasibility, determined by the proportion of patients who completed four cycles of the combination chemotherapy. Adverse events were graded according to National Cancer Institute Common Toxicity Criteria (version 4.0). Median relapse-free survival time after surgery was calculated by analyzed by
P1.03-035 Efficacy of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC J. Bosch Barrera,1 E. Sais,1 S. Verdura,2 E. Cuyas,2 D. Roa,1 A. Hernández,1 A. Izquierdo,1 E. Teixidor,1 W. Carbajal,1 M. Lopez,3 J. Brunet,1 J.A. Menendez4 1Catalan Institute of Oncology. Hospital Universitari Dr. Josep Trueta, Girona/ES, 2Girona Biomedical Research Institute (Idibgi), Molecular Oncology Group, Salt/ES, 3Pharmacy Department, Catalan Institute of Oncology. Hospital Universitari Dr. Josep Trueta, Girona/ES, 4Procure (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona/ES Background: Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1e3, PDGFa and b, and FGFR1e3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy. The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exert significant anti-cancer effects in pre-clinical models. The oral use of the silibinin-containing nutraceutical Legasil® could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment. Method: Patients with stage IV NSCLC who failed 1 prior treatment were eligible for nintedanib/docetaxel combination. We present data of patients that received nintedanib plus docetaxel with or without combination with up to 5 capsules/day of Legasil®, which equated to a 630 mg/ day dose silibinin regimen, as complementary treatment. The nature of the interaction between nintedanib and silibinin was explored in a broad panel of human NSCLC cell lines. Result: Twenty-two patients were enrolled in the study: median age 63y (range: 44e74); male: 14. All the cases were non-squamous NSCLC. All patients had received first line therapy; 3 patients had 2 prior lines of treatment. The mean PFS was 1.82 months (95% confidence interval [CI] 1.39e2.26) for the nintedanib plus docetaxel combination (n¼7) versus 4.97 (95%CI 2.87e7.07) for the nintedanib, docetaxel and Legasil® triple combination (n¼15) (p¼0.02). No statistically significant differences in mean OS were observed between the two arms: 4.88 (95%CI 3.26e6.48) for nintedanib plus docetaxel versus 10.3 (95%CI 5.85e14.76) for nintedanib plus docetaxel plus Legasil® (p¼0.534). At the data cutoff in June 2017, 9 (41%) patients remained alive. A significant inverse correlation was found between nintedanib and silibinin sensitivity among NSCLC cell lines. The combined treatment of nintedanib and silibinin produced unanticipated, synergistic cytotoxic effects in nintedanib-unresponsive NSCLC cells. Conclusion: There is a clinical and biological rationale for combining nintedanib and docetaxel with the silibinin-containing nutraceutical Legasil® in patients with advanced NSCLC, where few effective second-line treatment options are available. Keywords: silibinin, nintedanib, docetaxel
Journal of Thoracic Oncology
Vol. 12 No. 11S2
P1.03-036 Adjuvant Chemotherapy with Uracil-Tegafur for Pathological T1aN0M0 Lung Adenocarcinoma with Lymphatic Vessel Invasion Y. Kitamura, W. Nishio, H. Tanaka, K. Minami, H. Okuma, M. Yoshimura Chest Surgery, Hyogo Cancer Center, Akashi/JP Background: The aim of this retrospective study was to investigate the efficacy of adjuvant chemotherapy for patients in pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion. Method: We retrospectively collected data on 72 consecutive patients with pathological T1aN0M0 (the 7th edition of the UICC TNM stating system) lung adenocarcinoma with lymphatic or/and vessel invasion from January 2001 to December 2013. Adjuvant uracil-tegafur group were compared with control group. Overall survival (OS) and diseasefree survival (DFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Prognostic factors were evaluated using a Cox proportional hazard model. Result: Among the 72 patients, 21 patients (29.1%) were treated with adjuvant chemotherapy with uraciletegafur. No significant difference was found in patient characteristics between the two groups. In the 21 adjuvant chemotherapy and 51 control groups, the 5-year OS rates were 100% versus 80.8%, respectively; and the 5-year DFS rates were 88.2% versus 65.1% (p¼0.0138), respectively. Multivariate analysis revealed that adjuvant chemotherapy was only independent predictor of OS and DFS (p ¼ 0.014, 0.013, respectively). Conclusion: Adjuvant chemotherapy with uraciletegafur improves survival among patients with completely resected pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion. Our study suggests that pathological T1aN0M0 lung adenocarcinoma with lymphatic vessel invasion potentially benefits from adjuvant chemotherapy. Keywords: non-small cell lung cancer, adjuvant chemotherapy, Lymphatic vessel invasion
P1.03-037 A Phase II Study of Adjuvant Chemotherapy with Docetaxel plus Nedaplatin for Completely Resected Non-Small Cell Lung Cancer K. Teramoto,1 Y. Namura,2 K. Hayashi,2 K. Ishida,2 K. Ueda,2 K. Okamoto,2 R. Kaku,2 T. Hori,2 Y. Kawaguchi,2 T. Igarashi,2 M. Hashimoto,2 Y. Ohshio,2 S. Kitamura,2 M. Motoishi,3 Y. Suzumura,4 S. Sawai,3 J. Hanaoka,2 Y. Daigo1 1Department of Medical Oncology, Shiga University of Medical Science, Otsu/JP, 2 Department of Surgery, Shiga University of Medical Science, Otsu/JP, 3 Department of Thoracic Surgery, National Hospital Organization Kyoto Medical Center, Kyoto/JP, 4Department of Thoracic Surgery, Ijinkai Takeda General Hospital, Kyoto/JP Background: Nedaplatin, a cisplatin derivative, has similar activity to cisplatin for non-small-cell lung cancer (NSCLC). We previous reported that the combination chemotherapy of docetaxel plus nedaplatin was well tolerated in patients with advanced NSCLC. The purpose of this phase II study was to evaluate the feasibility of combination chemotherapy of docetaxel plus nedaplatin as adjuvant chemotherapy in patients with completely resected stage IB-IIIA NSCLC. Method: Following a radical surgery, patients were treated with docetaxel (60 mg/m2) and nedaplatin (80 mg/m2) on day 1 every four weeks up to four cycles. The primary endpoint was feasibility, determined by the proportion of patients who completed four cycles of the combination chemotherapy. Adverse events were graded according to National Cancer Institute Common Toxicity Criteria (version 4.0). Median relapse-free survival time after surgery was calculated by analyzed by