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1 Chicago と私 神戸大学医学部附属病院呼吸器内科小谷義一

2 米国臨床腫瘍学会がんの治療および予防の包括的な改善を目指し 1964 年に設立されたNPO 団体です 機関誌 Journal of Clinical Oncology は がん専門医にとって 極めて著名な必読誌となっており 毎年米国にて開催されるAnnual Meeting ( 年次総会 ) は5 日間でおよそ30,000 人以上の参加者を世界中から集めます

3 年々参加人数が増加して シカゴでしか開催できなくなりました

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8 履歴書 1992 年 3 月 神戸大学卒業 同年 6 月 神戸大学医学部附属病院研修医 呼吸器内科入局 1993 年 6 月 豊岡病院組合立日高病院 1995 年 4 月 神戸大学大学院医学研究科 1999 年 1 月 愛仁会高槻病院 1999 年 6 月 兵庫県立成人病センター 2005 年 3 月 神戸大学医学部附属病院

9 研修医時代 大学病院ではおとなしく日高病院では好き勝手に 入院患者全員に心エコー 採血は大腿静脈から 産婦人科手術にも入る 院内の呼吸器関連の患者を集める

10 大学院時代 気管支喘息の遺伝子に関する研究誰も指導者ない状況机もありませんでした 循環器内科 ( 現在総合内科 ) 金澤先生が私の実験の師匠ですいまも頭があがりません 2 年間はまったくデータでず夕方バイトから帰って 子供を風呂に入れてから 泣きそうになりながら実験を深夜にしてましたしかしポケベル ( 当時携帯はあんまり普及してませんでした ) が鳴らない平和な 3 年半でした

11 大学院時代 2 なんとかデータをまとめて当時大学の No.2であったBossから アメリカで発表しよう といわれました 1998 年 7 月 American Thoracic において呼吸器内科 10 年ぶりの海外発表 (Chicago1 回目 ) どきどきはしましたが 非常に感動 翌年から毎年みんなが発表するように

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13 2002 年 12 月 2003 年 6 月に開催される ASCO での WJTOG9902( 多施設共同試験 ) の発表の指名を受けました わずか肺癌を専門にして 2 年半でのでき事でした ASCO2003@Chicago (Chicago2 回目 ) Poster discussion session に

14 Phase II study of cisplatin, etoposide and concurrent thoracic radiotherapy (TRT) followed by irinotecan and cisplatin in patients with limited stage small-cell lung cancer (SCLC) Yoshikazu Kotani, Yoshiki Takada, Kaoru Matsui, Kenji Eguchi, Yukito Ichinose, Shinzo Kudoh, Kazuhiko Nakagawa, Minoru Takada, Hiroshi Saito, Yutaka Ariyoshi. For The West Japan Thoracic Oncology Group (WJTOG)

15 Treatment Schema Multi-institutional, phase II study PE+TRT CDDP 80 mg/m 2 D1 VP mg/m 2 D1-3 TRT 1.5 Gy bid, 45 Gy CPT-11+CDDP CPT mg/m 2 D1, 8, 15 CDDP 60 mg/m 2 D1 every 4 weeks 3 cycles WJTOG9902

16 Survival Survival rate (%) yr-survival rate 86.4% 2yr-survival rate 50.7% n= years WJTOG9902

17 質問されたこと 1.neutropenic fever? 2.RT の後 どれだけあけて CPT がはいるのか? 3.phaseIII はいつ始まるのか? 4.Dr.Choy にはこちらから声かけました 1. なぜ PE なのか?CPT を最初からつかえばいいのに アメリカではふつうだよ 2. 誰が企画した syudy だ? 5.MST は? 6.CDDP は 60mg なのはなぜ? 7.PE は 4 週間? 8. 下痢にはどんな治療してる? 9. あなたはどんな position で仕事してる?( これは勧誘でしょうか?) 10.CPT で小さくしてから PE で RT するなんてのはどう? 11. 食道炎がすごい少ないよ 僕のところ ( アメリカでした ) では 50% はこえるよ 12.CPT は 3week,4week? PE と phaseiii 戦わせるなら 同じ 3week のほうがいいのに 13. なぜ 1 コースでこんなに落ちてるの? 14.CT はどのタイミングでとるの? アメリカでは 2 ヶ月に 1 回だよ 15.RT は毎日? それとも土日は休み? 16.Good job! WJTOG9902

18 兵庫県立成人病センター時代 癌の臨床試験をしようとなりまして ED-SCLCに対してAMR+ETP+CDDPという今考えると殺人的なレジメンを考案してWJTOG 提出 プレゼンこれがそののちの師匠になる根来俊一先生の目にとまりJCOGで試験をすることに

19 神戸大学医学部附属病院 JCOG0509 研究事務局を引き続き継続 2011 年 12 月試験中止勧告 2012 Negative studyなのでposterだろうと思ったらなんとoral abstractに選ばれてしまいました Chicago 5 回目!

20 ( A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509. Yoshikazu Kotani, Miyako Satouchi, Masahiko Ando, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Yukito Ichinose, Yuichiro Ohe, Makoto Nishio, Toyoaki Hida, Koji Takeda, Tatsuo Kimura, Koichi Minato, Akira Yokoyama, Shinji Atagi, Taro Shibata, Haruhiko Fukuda, Tomohide Tamura, Nagahiro Saijo, Japan Clinical Oncology Group

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24 Study Design ( ED-SCLC yrs PS 0-1 Stratification PS institution sex Sample size n= 282 (n= 141 per Arm) R A N D O M I Z E IP irinotecan 60 mg/m 2 D1,8,15 cisplatin 60 mg/m 2 D1 Q4 weeks x 4 cycles amrubicin 40 mg/m 2 D1-3 cisplatin 60 mg/m 2 D1 Q3 weeks x 4 cycles AP PCI for CR cases 2.5Gy 10 Fr The planned sample size of 282 was determined based on a one-sided alpha of 5%, a power of 70% and a non-inferiority margin of hazard ratio (HR) in overall survival as 1.31.

25 Proportion surviving(%) Overall Survival 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% at 2nd interim analysis (cutoff date: May/23/2011) IP AP Pts Events Median(m) [95% CI] IP [ ] AP [ ] HR* : %CI , non-inferiority one-sided p= Survival time(months) *stratified Cox regression, with PS and sex as strata DSMC recommended early publication because the hazard ratio of AP to IP was larger than non-inferiority margin of (

26 Summary Overall survival of AP was much worse than that of IP (MST: 15.0 m vs18.3 m) and the HR was 1.41(multiplicity adjusted 96.3% CI: ). The non-inferiority of AP to IP was not demonstrated. Grade 4 neutropenia (22.5% vs. 79.3%) and G3-4 febrile neutropenia (10.6% vs. 32.1%) was higher in AP arm, while G3-4 diarrhea (7.7% vs.1.4%) was higher in IP arm. Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, ; P=0.227).

27 Conclusions Irinotecan plus cisplatin remains the standard treatment for ED-SCLC.

28 Acknowledgement We express our appreciation to all the participating patients, their families and investigators. National Cancer Center Hospital Kinki University School of Medicine Shizuoka Cancer Center National Kyushu Cancer Center National Cancer Center East Hospital Cancer Institute Hospital of Japanese Foundation for Cancer Research Aichi Cancer Center Osaka City General Hospital Osaka City University Hospital Hyogo Cancer Center Gunma Cancer Center Niigata Cancer Center Hospital NHO Kinki Chuo Chest Medical Center Saitama Cancer Center Asahikawa Medical Center Hokkaido Cancer Center Gifu Municipal Hospital Kanagawa Cancer Center Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Kumamoto Regional Medical Center Tochigi Cancer Center National Center for Global Health and Medicine Hospital Yokohama Municipal Citizen s Hospital Hyogo Collage of Medicine Shikoku Cancer Center Nishigunma Hospital Tokyo Metropolitan Cancer and Infection diseases Center Komagome Hospital KKR Sapporo Medical Center Aichi Cancer Center Aichi Hospital Kobe City Medical Center General Hospital Tohoku University Yamagata Prefectural Central Hospital Osaka General Medical Center Yamaguchi-Ube Medical Center JCOG data center This study was supported in part by the National Cancer Center Research and Development Funds(23- A-16 and 23-A-18), the Grant-in-Aid for Cancer Research (17S-2, 17S-5, 20S-2, and 20S-6) from the Ministry of Health, Labour and Welfare of Japan, and in part by the contract of periodical safety reports for AMR to Dainippon Sumitomo Pharma Co., Ltd.

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31 一応の仕事の完了 アメリカでも学会はChicago ばっかりでしたただし人生の節目にはいつも Chicagoがあったなあと思います

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研究開発分担者 2 ( 日本語 ) 国立研究開発法人国立がん研究センター中央病院外来医長堀之内秀仁所属役職氏名 : ( 英語 )National Cancer Center Hospital/Department of Thoracic Oncology Assistant Hidehito Hor

研究開発分担者 2 ( 日本語 ) 国立研究開発法人国立がん研究センター中央病院外来医長堀之内秀仁所属役職氏名 : ( 英語 )National Cancer Center Hospital/Department of Thoracic Oncology Assistant Hidehito Hor ( 報告様式 4) 課題管理番号 16ck0106072h0003 平成 29 年 3 月 31 日 平 28 年度委託研究開発成果報告書 I. 基本情報 事業名 : ( 日本語 ) 革新的がん医療実用化研究事業 ( 英語 )Practical Research for Innovative Cancer Control 研究開発課題名 : ( 日本語 ) 高齢者進行非扁平上皮非小細胞肺癌に対する標準的化学療法の確立に関する研究

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