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K. Kiura



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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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      P1.10-020 - Dose adjustment of single agent amrubicin in lung cancer patients with impaired hepatic function (ID 1348)

      09:30 - 09:30  |  Author(s): K. Kiura

      • Abstract

      Background
      The pharmacokinetics (PK) of amrubicin (AMR) in lung cancer patients with impaired hepatic function have not been reported. The objectives of this study were to evaluate the PK of AMR and its major metabolite, amrubicinol (AMR-OH), in lung cancer patients with or without impaired hepatic function, and to assess the validity of dose adjustment of AMR based on hepatic function.

      Methods
      Eligibility criteria included the presence of histologically or cytologically proven lung cancer, an ECOG PS of 0 to 2, age 20 to 70 years old, and no evidence of hepatitis B virus infection. The dose was adjusted from 25 to 45 mg/m[2]/day (iv, days 1-3, q3w) based on the history of prior treatment and baseline values of total bilirubin (T-bil), AST and ALT (Table 1). Figure 1

      Results
      Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) were enrolled. Terminal half-life (t~1/2~) and clearance of AMR in plasma, and t~1/2~ of AMR-OH in blood did not differ between the two arms. Area under the curve (AUC~0-24~) of AMR in plasma and AUC~0-120~ of AMR-OH in blood in arm I were similar or lower compared to those in arm N (Table 2). The dose-adjusted AUCs of AMR and AMR-OH did not show a tendency to increase with increases in baseline T-bil, AST and ALT. Two deaths occurred in arm I (one due to disease progression, and the other due to an unspecified reason), but the toxicities in arm I were not severe compared with those in arm N. Figure 1

      Conclusion
      These data show the validity of dose adjustment of AMR in patients with impaired hepatic function.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-016 - Perioperative nutrition of induction chemoradiotherapy followed by surgery in locally advanced non-small lung cancer patients (ID 1411)

      09:30 - 09:30  |  Author(s): K. Kiura

      • Abstract

      Background
      Induction chemoradiotherapy (CRT) followed by surgery (iCRT) is one of treatment strategies for locally advanced non-small cell lung cancers (NSCLCs). We have previously reported its feasibility and good clinical outcome with approximately 60% of 5-year overall survival rate. .Perioperative nutritional status,is considered as one of important factors for improved clinical outcome after surgery and other treatments. Here, we investigated the perioperative nutritional status in NSCLC patients treated by iCRT (CRT group) to evaluate the influence of nutritional variables on clinical outcome by comparing that in NSCLC patients with simple pulmonary resection without CRT (non-CRT group) .

      Methods
      Thirty-three consecutive patients with locally adcanced NSCLC who underwent iCRT from January 1, 2009, until December 31, 2011 at our institute were included in this study. The regimen of CRT was two cycles of docetaxel (40 mg/m[2]) plus cisplatin (40 mg/m[2]) with concurrent radiotherapy (46 gray) and the surgery was performed within 6 weeks of completing induction CRT. We compared nutrition-related factors and clinical outcome in 33 iCRT patients with those in 58 consecutive NSCLC patients who underwent lobectomy during January 1 to December 31, 2011 at out institute. .As for blood nutritional factors, total lymphocyte count (TLC), albumin (Alb), total cholesterol (T-cho), choline esterase (ChE), were examined. The prognostic nutritional index (PNI) was also calculated by Alb and TLC. Each nutrition-relatd factors were examined 1) before CRT, 2) before surgery and 3) one month after surgery.

      Results
      Median age of CRT group (61 years old) was significantly younger than that of non-CRT group (69 years old). Twenty-one males and 12 females and 44 males and 14 females were enrolled in CRT and non-CRT groups, respectively. Before any treatment, no significant difference was observed in body mass index and any blood nutritional factors in both groups. After induction CRT, TLC was significantly decreased, and additionally, Alb, T-cho, and ChE were significantly decreased after surgery comparing with those before surgery (after CRT). As for preoperative status in both groups, TLC, Alb and PNI were significantly lower in CRT group than in non-CRT group. Regard with surgery, extended surgery, operating time, and blood loss was significantly heavier in CRT group than in non-CRT group. Perioperative mortality rate was 0% in both groups and the frequency of post-operative complication was similar in both groups (51% and 41% in CRT and non-CRT groups, respectively). The length of hospital stay after surgery was significantly longer in CRT group (median 23 days) than in non-CRT group (median 14 days). Among CRT group, patients with loiw PNI index could not administrate adjuvant chemotherapy.

      Conclusion
      Perioperative nutritional status, especially TLC, is suppressed after CRT and moreover after surgery. Suppression of nutritional status continued one month after surgery with induction CRT and severe suppression of nutritional status disturbs further treatment such as adjuvant chemotherapy.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 2
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      P2.09-005 - Cisplatin, S-1 and concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: A phase II study of Okayama Lung Cancer Study Group 0501 (ID 1202)

      09:30 - 09:30  |  Author(s): K. Kiura

      • Abstract

      Background
      Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small-cell lung cancer (LA-NSCLC). However, its cure rate remains unsatisfied, and further improvement in the treatment outcome is strongly warranted. S-1 (S), an oral fluoropyrimidine, is a new active agent possessing a radio-sensitizing effect. Additionally, combining S and cisplatin (P) offered an active and safe regimen for metastatic non-small-cell lung cancer. The objective of this study was to assess the efficacy and safety of S plus P with concurrent thoracic radiotherapy (TRT) for LA-NSCLC.

      Methods
      Patients with stage IIIA/IIIB, aged ≤75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was respsonse rate, and required sample size was 48 patients.

      Results
      Between 2006 and 2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1, 36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). At a median follow-up of 54 months for the surviving patients, median progression-free survival and median survival time were 9.3 months and 31.3 months, respectively. No difference in efficacy (response and survivals) was observed stratified by histology (sq vs. non-sq). Toxicities were generally mild, including G3/4 neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia (8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No toxic deaths have occurred.

      Conclusion
      This chemoradiotherapy regimen yielded a favorable overall survival data. Also, it was well-tolerated in patients with LA-NSCLC as compared with concurrent docetaxel plus P with TRT therapy especially in term of TRT-related toxicities.

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      P2.09-011 - Tumor arising from lower lobes is a poor prognostic factor in non-small cell lung cancer patients with N2 disease treated with induction chemoradiotherapy (ID 2239)

      09:30 - 09:30  |  Author(s): K. Kiura

      • Abstract

      Background
      Trimodality therapy consisting of induction chemoradiotherapy (CRT) followed by surgery can be one of the treatment options for locally advanced non-small cell lung cancer (NSCLC). While recent randomized phase III trials failed to demonstrate a benefit from the addition of surgery in the entire population, the subset analysis of the intergroup trial 0139 indicates that trimodality therapy is beneficial for population who did not undergo pneumonectomy. This result strongly suggests that the status of disease may influence the prognosis even in same stage population. Thus, identifying prognostic factors and their inclusion in stratification are critical for the appropriate randomized study. In this study, we retrospectively examined the prognostic impact of tumor location in NSCLC patients with clinical (c-) N2 disease who underwent trimodality therapy in our institute.

      Methods
      Among patients who underwent induction CRT followed by surgery between 1999 and 2011 at our institution, a total of 76 NSCLC patients with c- N2/3 stage III were enrolled for this retrospective study. Induction CRT basically consisted of docetaxel and cisplatin with concurrent radiation at a dose of 40 - 60 Gray.

      Results
      A total of 76 patients consisted of 53 male and 23 female, 43 adenocarcinomas and 33 non-adenocarcinomas, and 44 c-Stage IIIA and 32 c-Stage IIIB. Primary tumors were located in right upper lobe for 33 patients, right middle lobe for 5, right lower lobe for 11, left upper lobe for 20, and left lower lobe for 7. For all population, lower lobe tumors showed significantly shorter overall survival (OS) and disease-free survival (DFS) times compared to non-lower lobe tumors (OS, p = 0.022; DFS, p = 0.0007). In a multivariate analysis, tumor location was independent prognostic factor for poor prognosis. Limited to pathologically proven N2/3 disease before induction CRT (n = 36), location of lower lobe tend to be poor prognosis compared to other location (OS, p = 0.068; DFS, p = 0.0075).

      Conclusion
      We showed that tumor arising from lower lobes is a poor prognostic factor in NSCLC patients with N2 disease treated with induction CRT. The status of tumor location should be considered in stratification in randomized trails that estimate the impact of the trimodality therapy.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-034 - One-year follow-up of a Phase I/II study of a highly selective ALK inhibitor CH5424802/RO5424802 in ALK-rearranged advanced non-small cell lung cancer (NSCLC) (ID 2591)

      09:30 - 09:30  |  Author(s): K. Kiura

      • Abstract

      Background
      CH5424802 is a novel tyrosine-kinase inhibitor that selectively inhibits ALK as well as secondary ALK mutations including L1196M. The preliminary results of the Phase I/II study (Lancet Oncol. 2013; 14: 590–8) showed that CH5424802 was active in the CNS and achieved a 93.5% objective response rate by RECIST in crizotinib-naïve NSCLC patients with a median follow-up of 7.6 months (range, 3.4–11.3). Here we report the 1-year follow-up results after the last patient enrolled in the Phase II analysis.

      Methods
      Patients with ALK-rearranged advanced NSCLC, who progressed after ≥1 prior chemotherapy regimens and who were naïve to any ALK inhibitors, received CH5424802 300 mg orally twice daily in the Phase II portion of the study. ALK fusion gene expression was confirmed by IHC and FISH or by RT-PCR at central laboratories. Tumor assessment was performed every cycle (21 days) until Cycle 4 and every 2 cycles thereafter with RECIST ver. 1.1.

      Results
      As of April 18, 2013, 46 patients had been treated with CH5424802 in the Phase II portion: median age, 48 years (range, 26–75); male/female, 22/24; ECOG PS 0/1, 20/26; never-smoker, 59%; ≥2 prior chemotherapy regimens, 52%. The objective response rate remains the same as previously reported, 93.5% (95% CI: 82.1% to 98.6%). At 1-year follow-up, a total of 7 patients (15%) had achieved a complete response. The median progression-free survival had not been achieved, and the 1-year progression-free rate (PFR) was 83% (95% CI: 68% to 92%). 34/46 patients were still on study treatment, and the median treatment duration had passed 14.8 months. CH5424802 also shows promising efficacy in the CNS: of 14 patients with baseline brain metastasis, 9 remained in the study without CNS or systemic progression for >12 months, with 6 of them exceeding 16 months. The other 5 patients with baseline CNS metastasis had no CNS progression during CH5424802 treatment. One of these patients discontinued the study due to AE, and the remaining 4 patients had systemic progression. The safety profile remains similar to that previously reported, with no patient requiring dose reduction.

      Conclusion
      CH5424802 demonstrated a high 1-year PFR of 83% and promising CNS activity. CH5424802 could be a novel therapeutic option for the treatment of ALK-rearranged NSCLC.