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Hirotoshi Dosaka-Akita



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    MA13 - Going Back to the Roots! (ID 139)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA13.10 - A Phase II Study of Carboplatin and Nab-Paclitaxel for Advanced Non-Small Cell Lung Cancer with Interstitial Lung Disease (HOT1302) (Now Available) (ID 990)

      14:00 - 15:30  |  Author(s): Hirotoshi Dosaka-Akita

      • Abstract
      • Presentation
      • Slides

      Background

      Because of the high risk of exacerbation of pre-existing interstitial lung disease (ILD), patients with concomitant advanced non-small cell lung cancer (NSCLC) and ILD have been excluded from most clinical trials of chemotherapy, despite the high prevalence (around 10%) of all NSCLC cases. This study prospectively evaluated the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin in advanced NSCLC patients with pre-existing ILD.

      Method

      Enrolled patients had treatment-naïve, advanced NSCLC with pre-existing ILD. Patients received 100 mg/m2nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks for 4-6 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS) and overall survival (OS). The interactions between histology [Squamous (Sq) vs. Non-Squamous (Non-Sq)] and treatment outcomes were also investegated.

      Result

      Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had an adenocarcinoma, followed by 15 (41.7%) squamous cell carcinoma, and 5 (13.9%) non-small cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR, the primary endpoint, was 55.6% (95% confidence interval [CI]: 39.6-70.5%). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2 months) and 15.4 months (95% CI: 9.4-18.7 months), respectively. There was no significant difference between two groups, however, numerically better treatment outcomes were observed in the Sq group: the ORR was 66.7% (95% CI: 41.7–84.8%) in the Sq group compared with 47.6 % (95% CI: 28.3–67.6%) in the Non-Sq group (P =0.254); median PFS was 8.2 months (95% CI: 4.0–10.2 months) in the Sq group vs. 4.1 months (95% CI: 3.3-5.4 months) in the Non-Sq group (HR, 0.60 [95% CI, 0.30–1.20]; p=0.15); median OS was 16.8 months (95% CI: 9.8 months–not reached) in the Sq group vs. 11.9 months (95% CI: 7.3-17.4 months) in the Non-Sq group (HR, 0.56 [95% CI, 0.24–1.28]; p=0.17). Two patients (5.6%) experienced grade ≥2 pneumonitis and one patient (2.8%) died.

      Conclusion

      This is the first prospective phase 2 study of weekly nab-paclitaxel in combination with carboplatin in advanced NSCLC patients with pre-existing ILD. This treatment showed favorable efficacy and was well tolerated.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-53 - Immunoproteasome as a Potential Therapeutic Target in Cisplatin-Resistant Small and Non-Small Cell Lung Cancer (ID 365)

      10:15 - 18:15  |  Author(s): Hirotoshi Dosaka-Akita

      • Abstract
      • Slides

      Background

      Cisplatin resistance remains a major problem in the treatment of both non-small (NSCLC) and small cell lung cancer (SCLC). Cisplatin has been reported to cause DNA damages and oxidative stress leading to numerous changes in cell physiology in transcriptional and protein levels. Thus, cisplatin-resistant (CR) cancer cells could alter the proteasome expression to eliminate abnormal proteins induced by cisplatin. Here, we examined the status of proteasomes in CR lung cancer cells and whether proteasomes could be a therapeutic target to overcome cisplatin resistance in lung cancer.

      Method

      CR variants were established from three NSCLC cell lines (A549, H1299, and H1975) and two SCLC cell lines (SBC3 and SBC5) in our laboratory. The activity of 20S proteasome core enzyme, the expressions of proteasome subunits, and the sensitivity of immunoproteasome inhibitors, Carfilzomib (CFZ) and PR957, were examined in these CR cells.

      Result

      The CR cells showed higher activity of 20S proteasome core enzyme compared with the parent cell counterparts. Quantitative RT-PCR and Western blot analysis revealed that all of the five CR cells had significantly higher expressions of immunoproteasomes, including PSMB8 and PSMB9, while no remarkable changes were observed in the expressions of standard proteasomes. H1299 and SBC3 cells became more sensitive to CFZ and PR957 when acquiring resistance to cisplatin. CFZ induced cell cycle G2/M arrest and apoptosis in CR variants of H1299 and SBC3.

      Conclusion

      Immunoproteasome can be a therapeutic target in a portion of cisplatin-resistant both of NSCLC and SCLC.

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