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H. Senju



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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-015 - The Relationship between the UGT1A1*27 and UGT1A1*7 Genetic Polymorphisms and Irinotecan-Related Toxicities in Patients with Lung Cancer (ID 7500)

      09:30 - 09:30  |  Author(s): H. Senju

      • Abstract

      Background:
      Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1), UGT1A7, and UGT1A9 genes are associated with interindividual differences in irinotecan toxicities. Purpose: To evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy.

      Method:
      The eligibility criteria were as follows: lung cancer patients who were scheduled to undergo irinotecan therapy, aged ≥20 years, and had a performance status of 0-2. After informed consent had been obtained, patients were enrolled, and their blood was collected and used to examine the frequency of the UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the drug concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy.

      Result:
      Thirty-one patients were enrolled. The patients’ characteristics were as follows: male/female = 25/6, median age (range) = 71 (55-84), stage IIB/IIIA/IIIB/IV = 2/6/11/12, and Ad/Sq/Sm/Oth = 14/10/3/4. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. There were no homozygous or complex heterozygous polymorphisms. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those seen in the wild-type patients. SN-38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with the UGT1A1*27 or UGT1A1*28 polymorphism. No severe myelotoxicity was seen in the patients with UGT1A1*7.

      Conclusion:
      UGT1A1*27 and UGT1A1*7 are both rare gene polymorphisms. UGT1A1*27 can occur separately from UGT1A1*28 in some circumstances and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan-induced toxicities, and UGT1A1*29 seems to have little clinical impact.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-045 - A Retrospective Analysis of Nivolumab-Related Pneumonitis in Non-Small Cell Lung Cancer Patients (ID 10051)

      09:30 - 09:30  |  Author(s): H. Senju

      • Abstract

      Background:
      Nivolumab is a human IgG4 monoclonal antibody that targets programmed cell death-1 (PD-1). In advanced non-small-cell lung cancer patients, nivolumab has been well tolerated. However, some patients develop nivolumab-related pneumonitis.

      Method:
      We retrospectively analyzed the clinical features and prognosis of nivolumab-related pneumonitis in non-small cell lung cancer patients in the institutions of the Nagasaki Thoracic Oncology Group.

      Result:
      From January 1, 2016 to May 31, 2017, 101 non-small cell lung cancer patients were treated with nivolumab monotherapy and 8 patients (7.9%) developed nivolumab-related pneumonitis. 7 were male, and 1 was female, with a median age of 70 years. The histological subtype was squamous cell carcinoma in 3 patients, non-squamous cell carcinoma in 5 patients. 6 patients were stage III or IV. 2 patients were postoperative recurrence. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 6 patients and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The median time from nivolumab treatment initiation to development of pneumonitis was 8.5 weeks (range, 1-16). 2 patients of AIP/ARDS pattern developed pneumonitis within 2 weeks. Bronchoalveolar lavage conducted in 4 patients and bronchoalveolar lavage fluid revealed elevation of lymphocyte in all patients. All patients received corticosteroids. 6 patients of COP pattern had clinical and radiographic improvement. 2 patients of AIP/ARDS pattern worsened clinically and died during the course of pneumonitis treatment. One of patient experienced recurrent pneumonitis in the course of corticosteroid taper.

      Conclusion:
      We retrospectively analyzed the clinical features and prognosis of nivolumab-related pneumonitis in non-small cell lung cancer patients. Nivolumab-related pneumonitis showed variable onset and radiographic patterns. COP pattern was most common. Most patients were successfully treated with corticosteroids, but AIP/ARDS pattern was risk of poor prognosis.