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Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan

Yuji Minegishi, Akihiko Gemma, Sakae Homma, Kazuma Kishi, Arata Azuma, Takashi Ogura, Naoki Hamada, Hiroyuki Taniguchi, Noboru Hattori, Yasuhiko Nishioka, Kiminobu Tanizawa, Takeshi Johkoh, Takuma Yokoyama, Kazutaka Mori, Yoshio Taguchi, Masahito Ebina, Naohiko Inase, Koichi Hagiwara, Hiroshi Ohnishi, Hiroshi Mukae, Yoshikazu Inoue, Kazuyoshi Kuwano, Hirofumi Chiba, Ken Ohta, Yoshinori Tanino, Fumikazu Sakai, Yukihiko Sugiyama for the Diffuse Lung Diseases Research Group
ERJ Open Research 2020 6: 00184-2019; DOI: 10.1183/23120541.00184-2019
Yuji Minegishi
1Dept of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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  • ORCID record for Yuji Minegishi
  • For correspondence: yminegis@nms.ac.jp
Akihiko Gemma
1Dept of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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Sakae Homma
2Dept of Respiratory Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
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Kazuma Kishi
3Dept of Respiratory Medicine, Respiratory Center Toranomon Hospital, Tokyo, Japan
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Arata Azuma
1Dept of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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Takashi Ogura
4Dept of Respiratory medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
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Naoki Hamada
5Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Hiroyuki Taniguchi
6Dept of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan
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Noboru Hattori
7Dept of Molecular and Internal Medicine Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
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Yasuhiko Nishioka
8Dept of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
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Kiminobu Tanizawa
9Dept of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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  • ORCID record for Kiminobu Tanizawa
Takeshi Johkoh
10Dept of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Teachers, Hyogo, Japan
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Takuma Yokoyama
11Dept of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan
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Kazutaka Mori
12Second Dept of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Yoshio Taguchi
13Dept of Respiratory Medicine, Tenri Hospital, Tenri, Japan
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Masahito Ebina
14Tohoku Medical and Pharmaceutical University School of Medicine, Dept of Respiratory Medicine, Sendai, Japan
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Naohiko Inase
15Tokyo Medical and Dental University, Tokyo, Japan
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Koichi Hagiwara
16Division of Pulmonary Medicine, Jichi Medical University, Shimono, Japan
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Hiroshi Ohnishi
17Dept of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan
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Hiroshi Mukae
18Dept of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Yoshikazu Inoue
19Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
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  • ORCID record for Yoshikazu Inoue
Kazuyoshi Kuwano
20Division of Respiratory Diseases, Dept of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Hirofumi Chiba
21Dept of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Ken Ohta
22Japan Anti-Tuberculosis Association Fukujuji Hospital, Tokyo, Japan
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Yoshinori Tanino
23Dept of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan
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Fumikazu Sakai
24Dept of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, Saitama, Japan
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Yukihiko Sugiyama
25Nerima-Hikarigaoka Hospital, Tokyo, Japan
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  • Article
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  • FIGURE 1
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    FIGURE 1

    Overall survival (OS) a and b) from second-line chemotherapy and c and d) from first-line chemotherapy of a and c) nonsmall cell lung cancer (NSCLC) and b and d) small cell lung cancer (SCLC), respectively. MST: median survival time.

Tables

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  • TABLE 1

    The incidence of acute exacerbation (AEx) of idiopathic interstitial pneumonias related to each first-line chemotherapy regimen

    RegimenPatientsAEx
    Carboplatin+paclitaxel140 (35.4%)12 (8.6%)
    Carboplatin+etoposide82 (20.7%)3 (3.7%)
    Cisplatin+etoposide38 (9.6%)4 (10.5%)
    Vinorelbine30 (7.6%)8 (26.7%)
    Cisplatin+UFT17 (4.3%)5 (29.4%)
    Carboplatin+vinorelbine10 (2.5%)0 (0%)
    Cisplatin+vinorelbine9 (2.3%)2 (22.2%)
    Docetaxel7 (1.8%)1 (14.3%)
    Carboplatin+docetaxel6 (1.5%)4 (66.7%)
    Cisplatin+docetaxel6 (1.5%)1 (1.7%)
    Gefitinib6 (1.5%)5 (83.3%)
    Others5110 (19.6%)
    Total39652 (13.1%)

    UFT: tegafur-uracil.

    • TABLE 2

      The association between acute exacerbation (AEx) of idiopathic interstitial pneumonias and each suspected cytotoxic agent

      AgentsPatientsAEx
      Cisplatin9115 (16.5%)
      Carboplatin25020 (8.0%)
      Etoposide1247 (5.6%)
      Paclitaxel14618 (12.3%)
      Vinorelbine5110 (19.6%)
      Docetaxel196 (31.6%)
      Gemcitabine61 (16.7%)
      Vindesine171 (5.9%)
      UFT175 (29.4%)
       Platinum-based regimen34135 (10.3%)
       Nonplatinum-based regimen#4913 (26.5%)

      UFT: tegafur-uracil. #: gefitinib was excluded.

      • TABLE 3

        Patient characteristics of the analysis of second-line chemotherapy

        AEAS#SAS#
        Subjects278180
        Age years median (range)69 (38–85)69 (38–83)
        Sex
         Male239 (86.0%)154 (85.6%)
         Female39 (14.0%)26 (14.4%)
        Histology
         AdC101 (36.3%)70 (38.9%)
         SqCC70 (25.2%)51 (28.3%)
         AdSqC1 (0.4%)1 (0.6%)
         NSCLC (NOS)32 (11.5%)14 (7.8%)
         SmCC74 (26.6%)44 (24.4%)
        Pattern of IIPs
         UIP146 (52.5%)89 (49.4%)
         Non-UIP103 (37.1%)66 (36.7%)
         Unclassified29 (10.4%)25 (13.9%)

        AEAS: acute exacerbation analysis set; SAS: survival analysis set; AdC: adenocarcinoma; SqCC: squamous cell carcinoma; AdSqC: adenosquamous carcinoma; NSCLC: nonsmall cell lung cancer; NOS: not otherwise specified; SmCC: small cell carcinoma; IIP: idiopathic interstitial pneumonia; UIP: usual interstitial pneumonia. #: AEAS was evaluated for acute exacerbation and objective response by second-line chemotherapy; SAS consisted of patients for which analysable survival information could be obtained.

        • TABLE 4

          The incidence of acute exacerbation (AEx) of idiopathic interstitial pneumonias related to each second-line chemotherapy regimen

          RegimenPatientsAEx
          Docetaxel72 (25.9%)11 (15.3%)
          Carboplatin+paclitaxel31 (11.1%)3 (9.7%)
          Vinorelbine24 (8.6%)6 (25%)
          Pemetrexed21 (7.6%)6 (28.6%)
          Amrubicin18 (6.5%)6 (33.3%)
          S-114 (5.3%)0 (0%)
          Nogitecan13 (4.9%)3 (23.1%)
          Carboplatin+etoposide15 (5.4%)0 (0%)
          EGFR-TKIs9 (3.2%)4 (44.4%)
          Paclitaxel7 (2.5%)1 (14.3%)
          Cisplatin+vinorelbine6 (2.2%)0 (0%)
          Irinotecan6 (2.2%)0 (0%)
          Others425 (12.5%)
          Total27845 (16.2%)

          EGFR-TKI: epidermal growth factor receptor tyrosine kinase inhibitor.

          • TABLE 5

            The response to second-line chemotherapy

            NSCLCSCLC
            Subjects20474
            Number of cycles median (range)3 (1–22)3 (1–6)
            Response
             CR01
             PR1518
             SD6817
             PD8323
             NE3815
            Overall response rate n1519
             % (95% CI)7.4 (3.8–10.9)25.7 (15.7–38.8)
            Disease control rate n8336
             % (95% CI)40.7 (33.9–49.6)48.6 (34.6–60.9)
            Introduction rate of third-line chemotherapy46.6%44.6%

            NSCLC: nonsmall cell lung cancer; SCLC: small cell lung cancer; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; NE: not evaluated.

            Supplementary Materials

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              Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

              Supplementary material 00184-2019.SUPPLEMENT

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            Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan
            Yuji Minegishi, Akihiko Gemma, Sakae Homma, Kazuma Kishi, Arata Azuma, Takashi Ogura, Naoki Hamada, Hiroyuki Taniguchi, Noboru Hattori, Yasuhiko Nishioka, Kiminobu Tanizawa, Takeshi Johkoh, Takuma Yokoyama, Kazutaka Mori, Yoshio Taguchi, Masahito Ebina, Naohiko Inase, Koichi Hagiwara, Hiroshi Ohnishi, Hiroshi Mukae, Yoshikazu Inoue, Kazuyoshi Kuwano, Hirofumi Chiba, Ken Ohta, Yoshinori Tanino, Fumikazu Sakai, Yukihiko Sugiyama
            ERJ Open Research Apr 2020, 6 (2) 00184-2019; DOI: 10.1183/23120541.00184-2019

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            Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan
            Yuji Minegishi, Akihiko Gemma, Sakae Homma, Kazuma Kishi, Arata Azuma, Takashi Ogura, Naoki Hamada, Hiroyuki Taniguchi, Noboru Hattori, Yasuhiko Nishioka, Kiminobu Tanizawa, Takeshi Johkoh, Takuma Yokoyama, Kazutaka Mori, Yoshio Taguchi, Masahito Ebina, Naohiko Inase, Koichi Hagiwara, Hiroshi Ohnishi, Hiroshi Mukae, Yoshikazu Inoue, Kazuyoshi Kuwano, Hirofumi Chiba, Ken Ohta, Yoshinori Tanino, Fumikazu Sakai, Yukihiko Sugiyama
            ERJ Open Research Apr 2020, 6 (2) 00184-2019; DOI: 10.1183/23120541.00184-2019
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