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K. Mochinaga



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-007 - Relationship between 5FU related enzymes and EGFR mutation status in non-small cell lung cancer treated with S-1 adjuvant therapy (ID 890)

      09:30 - 16:30  |  Author(s): K. Mochinaga

      • Abstract

      Background
      Anti-cancer effect of 5-fluorouracil (5FU) is affected by the expressions of 5FU related enzymes, such as dihydropyrimidine dehydrogenase (DPD) and thymidine synthase (TS) and orotate phosphoribosyltransferase (OPRT), in each tumor. On the other hand, anti-cancer effect of epidermal growth factor receptor tyrosine kinase (EGFR-TKI) is affected by EGFR mutation status in each tumor. In 2007, Suehisa and colleagues reported that adjuvant chemotherapy with uracil-tegafur, a fluorouracil prodrug, significantly prolonged survival rates among patients with EGFR wild-type adenocarcinoma but not among patients with EGFR mutant tumors. In this study, the correlation between 5FU related enzymes and EGFR mutation status was analyzed.

      Methods
      We analyzed 49 patients with primary NSCLC who were postoperatively treated with S-1, an oral fluorouracil anticancer prodrug composed of tegafur, CDHP, and potassium oxonate in the molar ratio 1:0.4:1. We then evaluated the relation between the EGFR mutation status, each of the 5FU related enzymes and various clinicopathological factors. In vitro, DPD mRNA and protein expression was investigated in various cell lines.

      Results
      Among the 49 cases (thirty adenocarcinoma (ADC), sixteen squamous cell carcinoma (SQCC), two adenosquamous carcinoma, and one carcinoid), EGFR mutation was observed only in ADC (12 patients; 24.5%). In immunohistochemical examination, 10 patients were DPD immune-positive (20.4%), 31 patients were OPRT immune-positive (63.3%), and 16 patients were TS immune-positive (32.7%). Three year disease free survival rate of single S-1 adjuvant therapy was 77.6%, and three year overall survival rate was 89.7%. DPD immune-positive cases were significantly correlated with EGFR mutation status (p = 0.003). In vitro, EGFR mutated cell lines showed high DPD mRNA and protein expression.Figure 1

      Conclusion
      High DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. This result indicates that 5FU might be effective for EGFR wild type tumors than mutant type tumor, and EGFR mutation status might be a potential poor predictive marker for treatment with 5FU drugs.

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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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      P1.10-038 - A phase II trial of the combination of gemcitabine and carboplatin as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. (Kenbyo 0601) (ID 2185)

      09:30 - 16:30  |  Author(s): K. Mochinaga

      • Abstract

      Background
      Background: Adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC) is recommended with survival benefit, however low compliance in recent clinical trials. Objectives: We conducted a phase II trial of gemcitabine(G) and carboplatin(C) regimen for patients with completely resected NSCLC and carboplatin is administrated on day 8 to reduce hematological toxicity especially thrombocytopenia.

      Methods
      Eligibility criteria included: PS(ECOG) 0-1, age≦75 years, p-stage IB-IIIA NSCLC is complexly resected (R0), adequate hematological liver renal and cardiac function. Regimen: G (1000mg/m2) d1 +8 and C (AUC 5, d8) q.3wks. Primary end point of this study is feasibility and secondary end points are toxicity, overall and disease-free survival.

      Results
      44 patients (20 male, 24 female) were included, median age 63 (40-71) years. Adenocarcinoma in 39, squamous cell ca. in 4, pleomorphic ca. in 1, and pathological stage IB in 25, IIA in 8, IIB in 5, and IIIA in 6 patients. Thirty-three patients (75%) completed the planned 4 cycles of GC therapy and 28 (64%) received the planned doses. Thirty-four percent of the patients had grade 3/4 neutropenia, 2 (6%) had thrombocytopenia, and the other 2 (6%) had anemia. Non-hematological adverse effects were infrequent and no treatment-related death was noted in this study.

      Conclusion
      Hematological toxicity, especially thrombocytopenia in this study is less than that in the standard administration of CG (C day1) regimen. We conclude that this regimen is feasible with sufficient compliance as adjuvant chemotherapy for completely resected stage IB-IIIA NSCLC patients.