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M. Shingyoji



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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-045 - Combination chemotherapy with bevacizumab, docetaxel and carboplatin for chemotherapy-naive patients with non-squamous cell lung carcinoma: Phase II study. (ID 2660)

      09:30 - 09:30  |  Author(s): M. Shingyoji

      • Abstract

      Background
      Some clinical studies suggested a possible advantage of bevacizumab combined with taxanes. Although carboplatin is slightly inferior to cisplatin in terms of survival, addition of bevacizumab to carboplatin may overcome this disadvantage. The aim of this study was to clarify the efficacy and safety of combination chemotherapy consisting of bevacizumab, docetaxel and carboplatin in the 1st line chemotherapy for non-squamous non-small cell lung cancer.

      Methods
      Patients who are untreatable with thoracic curative radiotherapy, with stage IIIB/IV non-squamous non-small cell lung cancer, age ranging from 20 to 74 years, PS 0 or 1, adequate organ functions, measurable lesions, and written informed consents were eligible. Combination chemotherapy consisting of bevacizumab (15 mg/kg), docetaxel (60 mg/m2) and carboplatin (AUC=6) on day 1 was administered every 3 weeks up to 6 cycles (induction phase). Unless PD, bevacizumab maintenance therapy was performed until PD (maintenance phase). The primary endpoint was median PFS to prove its superiority to the previous standard combination chemotherapy consisting of docetaxel and cisplatin with its historical median PFS of 4.6 months. With =0.05 and =0.20, calculated minimum sample size was 37, and the final determined sample size was 40. This trial was registered to the clinical trial registration system with the ID of UMIN000004524.

      Results
      Forty patients enrolled and 39 patients were analyzed. They included women in 31%, patients with PS of 0 in 67%, stage IV in 92%, EGFR mutations in 13% and unknown EGFR status in 8%. The median age was 62 years. The induction phase was delivered for 4 cycles in median (range: 1-6), and 21 patients (54%) received maintenance phase with median 4 cycles (range: 2-24). Frequent toxicities ≥ grade 3 during the induction phase in completely analyzed patients (n=32) included neutropenia (50.0%), anemia (9.4%), thrombocytopenia (9.4%), febrile neutropenia (25.0%) and hypertension (37.5%). Other toxicities ≥ grade 3 were cholecystitis, increased ALP, hyperpotassemia, proteinuria, diarrhea, appetite loss, nausea, constipation, infection, stomatitis, and cancer pain in 3.1%, respectively. Interim external reviews of 35 pts revealed ORR of 74% (26/35) and median PFS of 6.4 months (95% CI: 4.8-9.9).

      Conclusion
      The primary endpoint was met because the lower end of the 95%CI exceeded the threshold of 4.6 months. This combination chemotherapy seems promising in terms of safety and effectiveness, warranting phase III studies.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-001 - Lung Krueppel-like factor KLF2 improve post-operative prognosis of lung adenocarcinoma correlation with chemokine receptor CCR7 and genetical mutations of p53. (ID 30)

      09:30 - 09:30  |  Author(s): M. Shingyoji

      • Abstract

      Background
      Chemokines and chemokine receptors not only have the powerful ability in cancer metastasis and tumorigenesis, but also act as anti-tumorgenic ability. Lung Krueppel-like factor (LKLF, KLF2) is a member of the family of the Krueppel-like factors (KLFs).　KLF2 was initially described as a lung-specific transcription factor. KLF2 is reported to regulate some malignant cells. We examined and evaluated the effect of KLF2 on lung adenocarcinoma and the relationship of their mRNA expression with CCR7, EGFR and p53 genetical mutations in lung adenocarcinoma.

      Methods
      120 patients of stage I to IV with lung adenocarcinoma were included in this retrospective analysis. The expression of CCR7 and KLF2 mRNA expression in surgically resected lung adenocarcinoma specimens were examined and evaluated the relation to prognosis, the effect of EGFR and p53 genetical mutations. In addition the expression of CCR7 and KLF2 exprssion were analyzed with immunohistochemical analysis and measured their mRNA expression extracted from tissue sections of lung adenocarcinoma specimens by laser capture microdissection.

      Results
      High mRNA expression of KLF2 in lung cancer patients indicated significantly good prognosis than the groups of low expressions (p= 0.0066, HR= 2.008, 95% CI of ratio 1.215 to 3.319). The expression of KLF2 mRNA had relationships with CCR7, CCL21 and CCL19 mRNA expression in lung adenocarcinoma. Moreover the mRNA expression of KLF2 in lung adenocarcinoma specimens was influenced by the mutation of p53 mutation in lung cancer specimens. In addition the expression of KLF2 was confirmed with immunohistochemical analysis and was ditected mRNA expression extracted from tissue sections of lung adenocarcinoma specimens by laser capture microdissection.

      Conclusion
      We propose KLF2 as clinical good prognostic factors and that KLF2 has strong relation with CCR7, the ligands CCL19, CCL21 and p53 genetical mutation in lung adenocarcinoma.