論文 - 大家　基嗣

Efficacy and safety of sorafenib for advanced renal cell carcinoma

Tatsugami Katsunori, Oya Mototsugu, Kabu Koki, Akaza Hideyuki

Oncotarget 9 （ 27 ） 19406 - 19414 2018年04月

共著,  ISSN  1949-2553

　概要を見る

<p>Background: We retrospectively analysed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with renal impairment. Methods: Patients were divided into two groups by an estimated glomerular filtration rate (eGFR) cut-off of 45 mL/min/1.73 m². Background factors considered to affect prognosis were well balanced by propensity score matching between the groups. Demographics, dose modification, adverse events, tumour response, progression-free survival, and renal function (eGFR) were evaluated. Results: Among 935 and 2008 patients with an eGFR of < 45 and ≥45, respectively, 613 pairs were matched. The mean starting dose was significantly lower in patients with an eGFR of < 45; however, the mean daily dose, median treatment duration, progression-free survival, and tumour response were similar between the groups. In terms of safety, no significant differences were found in serious adverse events, although cytopaenia (16.6% vs 10.6%) and renal dysfunction (4.4% vs 0.7%) were higher in patients with an eGFR of < 45 than ≥45 in all adverse events. There were also no differences in dose modification, including dose reduction, dose int

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Efficacy and safety of sorafenib for advanced renal cell carcinoma: Real-world data of patients with renal impairment

Tatsugami K., Oya M., Kabu K., Akaza H.

Oncotarget （Oncotarget）  9 （ 27 ） 19406 - 19414 2018年04月

研究論文（学術雑誌）, 共著,  ISSN  1949-2553

　概要を見る

© Tatsugami et al. Background: We retrospectively analysed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with renal impairment. Methods: Patients were divided into two groups by an estimated glomerular filtration rate (eGFR) cut-off of 45 mL/min/1.73 m2. Background factors considered to affect prognosis were well balanced by propensity score matching between the groups. Demographics, dose modification, adverse events, tumour response, progression-free survival, and renal function (eGFR) were evaluated. Results: Among 935 and 2008 patients with an eGFR of < 45 and ≥45, respectively, 613 pairs were matched. The mean starting dose was significantly lower in patients with an eGFR of < 45; however, the mean daily dose, median treatment duration, progression-free survival, and tumour response were similar between the groups. In terms of safety, no significant differences were found in serious adverse events, although cytopaenia (16.6% vs 10.6%) and renal dysfunction (4.4% vs 0.7%) were higher in patients with an eGFR of < 45 than ≥45 in all adverse events. There were also no differences in dose modification, including dose reduction, dose interruption, and treatment discontinuation. Conclusion: Throughout the 12-month observation period, sorafenib in patients with an eGFR of < 45 and ≥45 showed similar safety and efficacy, and treatment was continued without affecting renal function.

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Continuation of axitinib for advanced renal cell carcinoma by the application of homecare urology-a case report and literature review

Yazawa S., Kato Y., Nakahara J., Miyata T., Oya M.

Japanese Journal of Cancer and Chemotherapy （Japanese Journal of Cancer and Chemotherapy）  45 （ 4 ） 639 - 642 2018年04月

共著,  ISSN  0385-0684

　概要を見る

© 2018 Japanese Journal of Cancer and Chemotherapy Publishers Inc. All rights reserved. A 56-year-old man with advanced RCC and a past medical history of type 2 diabetes underwent a radical left nephrectomy following a histological diagnosis of papillary RCC, G2, INF β, pT3, V1 in 1999. In 2008, sorafenib was started to treat multiple pulmonary metastases of RCC. In 2011, sorafenib was switched to sunitinib when radiologic progression was observed. In 2014, sunitinib was switched to axitinib when further radiologic progression was observed. In 2015, the patient was referred to Yazawa clinic for homecare urology when hospital visits became difficult due to cancer pain and bilateral lower-extremity muscle weakness. Cancer pain was controlled using acetaminophen and a fentanyl patch. During the administration of axitinib, a CTCAE grade 1 vocal disorder was detected. We reduced the axitinib dose from 10 mg to 6 mg, and valsartan and an antiflatulent were administered due to CTCAE grade 2 hypertension and diarrhea, respectively. Axitinib administration continued until the patient died. He had survived more than 11 years following the detection of lung metastasis. In this patient, a good balance between cancer treatment and palliative care was achieved through the application of homecare urology. In a super-aged society such as Japan, urologists with an awareness of Zaitaku Medicine, a Japanese style of homecare that provides continuing appropriate medical treatment and welfare support to patients with access barriers to hospital treatment to enable them to live out the remainder of their lives with dignity, may play a key role in the development of Zaitaku Medicine.

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial

大家 基嗣

The Lancet Oncology （The Lancet Oncology）  19 （ 4 ） 451 - 460 2018年04月

研究論文（学術雑誌）, 単著,  ISSN  1470-2045

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© 2018 Elsevier Ltd Background: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. Methods: The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Findings: Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the dose-expansion phase of the study. One dose-limiting toxicity of grade 3 proteinuria due to axitinib was reported among the six patients treated during the dose-finding phase. At the cutoff date (April 13, 2017), six (100%, 95% CI 54–100) of six patients in the dose-finding phase and 26 (53%, 38–68) of 49 patients in the dose-expansion phase had confirmed objective responses (32 [58%, 44–71] of all 55 patients). 32 (58%) of 55 patients had grade 3 or worse treatment-related adverse events, the most frequent being hypertension in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each. Six (11%) of 55 patients died before data cutoff, five (9%) due to disease progression and one (2%) due to treatment-related autoimmune myocarditis. At the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily. Interpretation: The safety profile of the combination avelumab plus axitinib in treatment-naive patients with advanced renal-cell carcinoma seemed to be manageable and consistent with that of each drug alone, and the preliminary data on antitumour activity are encouraging. A phase 3 trial is assessing avelumab and axitinib compared with sunitinib monotherapy. Funding: Pfizer and Merck.

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[Continuation of Axitinib for Advanced Renal Cell Carcinoma by The Application of Homecare Urology - A Case Report and Literature Review].

Yazawa S, Kato Y, Nakahara J, Miyata T, Oya M

Gan to kagaku ryoho. Cancer & chemotherapy 45 （ 4 ） 639 - 642 2018年04月

研究論文（学術雑誌）, 共著,  ISSN  0385-0684

　概要を見る

A 56-year-old man with advanced RCC and a past medical history of type 2 diabetes underwent a radical left nephrectomy following a histological diagnosis of papillary RCC, G2, INF b, pT3, V1 in 1999. In 2008, sorafenib was started to treat multiple pulmonary metastases of RCC. In 2011, sorafenib was switched to sunitinib when radiologic progression was observed. In 2014, sunitinib was switched to axitinib when further radiologic progression was observed. In 2015, the patient was referred to Yazawa clinic for homecare urology when hospital visits became difficult due to cancer pain and bilateral lower-extremity muscle weakness. Cancer pain was controlled using acetaminophen and a fentanyl patch. During the administration of axitinib, a CTCAE grade 1 vocal disorder was detected. We reduced the axitinib dose from 10 mg to 6 mg, and valsartan and an antiflatulent were administered due to CTCAE grade 2 hypertension and diarrhea, respectively. Axitinib administration continued until the patient died. He had survived more than 11 years following the detection of lung metastasis. In this patient, a good balance between cancer treatment and palliative care was achieved through the application of homecare urology. In a super-aged society such as Japan, urologists with an awareness of Zaitaku Medicine, a Japanese style of homecare that provides continuing appropriate medical treatment and welfare support to patients with access barriers to hospital treatment to enable them to live out the remainder of their lives with dignity, may play a key role in the development of Zaitaku Medicine.

泌尿器科在宅医療を導入しアキシチニブを継続し得た進行性腎がんの1例

矢澤 聰, 加藤 裕二, 中原 仁, 宮田 俊男, 大家 基嗣

癌と化学療法 （(株)癌と化学療法社）  45 （ 4 ） 639 - 642 2018年04月

共著,  ISSN  0385-0684

　概要を見る

症例は56歳、男性。1999年、左腎がんに対して根治的左腎摘除術を施行し、papillary RCC、G2、INFβ、pT3、V1でであった。2008年より多発肺転移に対してソラフェニブを開始した。2011年にprogressive disease(PD)となりスニチニブに変更、2014年にPDとなりアキシチニブ10mg/日に変更した。2015年よりがん疼痛と下肢筋力低下に伴い通院が困難となり、在宅医療を導入した。がん疼痛に対してはアセトアミノフェン4,000mg/日とフェンタニルテープ1mgでコントロール良好であった。アキシチニブ投与中の有害事象としては、CTCAE grade 2の高血圧を認め、バルサルタン80mgを開始した。またgrade 2の下痢を認め、アキシチニブ6mg/日への減量と整腸剤を投与し改善傾向を認め、アキシチニブを最期まで継続し得た。本症例において泌尿器科在宅医療の導入により、血管新生阻害薬の継続と緩和ケアとの両立が可能であった。超高齢社会における在宅医療に親和性の高い泌尿器科医が在宅医療の現場にでていくことで、新たな課題設定ならびに課題解決に取り組める可能性があると考えられた。(著者抄録)

ニボルマブ関連間質性肺炎寛解後も肺転移巣縮小を維持したmRCCの1例

岩佐 俊, 寺西 悠, 水野 隆一, 秋田 大宇, 額賀 重成, 大家 基嗣

泌尿器外科 （医学図書出版(株)）  31 （ 4 ） 439 - 443 2018年04月

共著,  ISSN  0914-6180

　概要を見る

症例は71歳男性。腹腔鏡下根治的左腎摘除術を施行した。術後に多発肺転移、右脛骨転移が出現し、1st lineとしてスニチニブを開始したがPDとなった。2nd lineとしてニボルマブ3mg/kgを開始して肺転移は縮小したが両側肺底部に器質化肺炎が出現し、ニボルマブ関連間質性肺炎の診断でニボルマブを中止、プレドニゾロン(PSL)を開始した。PSL投与により間質性肺炎のコントロールは良好で、ニボルマブ中止後も肺転移巣は9ヵ月間縮小を維持できている。(著者抄録)

IMAGING MASS SPECTROMETRY REVEALS CO-ACCUMULATION OF ALDOSTERONE AND 18-OXOCORTISOL WITH CYP11B2 IN PRE-ADENOMATOUS STATES OF PRIMARY ALDOSTERONISM

Sugiura Yuki, Takeo Emi, Shimma Shuichi, Yokota Mai, Higashi Tatsuya, Seki Tsugio, Oya Mototsugu, Kosaka Takeo, Nishikawa Tetsuo, Nishimoto Koshiro, Suematsu Makoto

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E23 - E23 2018年04月

共著, 査読有り,  ISSN  0022-5347

CAN UROLOGISTS INTRODUCE THE CONCEPT OF "OLIGOMETASTASIS" FOR METASTATIC BLADDER CANCER AFTER RADICAL CYSTECTOMY?

Koichiro Ogihara, Eiji Kikuchi, Keitaro Watanabe, Ryohei Kufukihara, Yoshinori Yanai, Kimiharu Takamatsu, Kazuhiro Matsumoto, Satoshi Hara, Masafumi Oyama, Tetsuo Monma, Takeshi Masuda, Shintaro Hasegawa, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E1043 - E1043 2018年04月

共著,  ISSN  0022-5347

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BIOINFORMATIC ANALYSIS IDENTIFIED CANDIDATE DRUGS FOR ANDROGEN SIGNALING THROUGH MODULATING ANDROGEN RECEPTOR AND ITS SPLICE VARIANTS

Hiroshi Hongo, Takeo Kosaka, Yota Yasumizu, Yasumasa Miyazaki, Eiji Kikuchi, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E852 - E852 2018年04月

共著,  ISSN  0022-5347

COULD ADJUVANT CHEMOTHERAPY HAVE ADDITIONAL THERAPEUTIC BENEFIT IN BLADDER CANCER PATIENTS TREATED WITH RADICAL CYSTECTOMY AND NEOADJUVANT CHEMOTHERAPY?

Minami Omura, Eiji Kikuchi, Koichiro Ogihara, Kyohei Hakozaki, Keishiro Fukumoto, Gou Kaneko, Yasumasa Miyazaki, Nobuyuki Tanaka, Suguru Shirotake, Kunimitsu Kanai, Kazuhiro Matsumoto, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E530 - E530 2018年04月

共著,  ISSN  0022-5347

THERAPEUTIC TARGETING OF TRANSCRIPTIONAL REPRESSOR BCL-6 FOR CASTRATION-RESISTANT PROSTATE CANCER THROUGH REPRESSING ANDROGEN RECEPTOR VARIANTS.

Hiroshi Hongo, Takeo Kosaka, Yota Yasumizu, Yasumasa Miyazaki, Eiji Kikuchi, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E850 - E850 2018年04月

共著,  ISSN  0022-5347

THE CLINICAL IMPACT OF INDURATION RESULTING FROM PURIFIED PROTEIN DEPRIVATION SKIN TEST IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH BACILLUS-CALMETTE GUERIN

Naoya Niwa, Eiji Kikuchi, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E1230 - E1230 2018年04月

共著,  ISSN  0022-5347

THE ANALYSIS OF EXPRESSION AND MOLECULAR MECHANISM FOR VASOHIBIN-2 IN PROSTATE CANCER

Yasumasa Miyazaki, Takeo Kosaka, Shuji Mikami, Hiroshi Hongo, Yota Yasumizu, Nobuyuki Tanaka, Eiji Kikuchi, Yasufumi Sato, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E857 - E857 2018年04月

共著,  ISSN  0022-5347

SWITCHING OF BACILLUS CALMETTE-GUERIN (BCG) STRAIN AT SECOND BCG THERAPY MAY REDUCE BCG-RELATED SIDE EFFECTS IN PATIENTS WITH BCG-RELAPSING TUMOR

Naoya Niwa, Eiji Kikuchi, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E100 - E100 2018年04月

共著,  ISSN  0022-5347

SUITABLE PATIENTS FOR SINGLE-PORT LAPAROSCOPIC ADRENALECTOMY: OPTIMAL CUT-OFF VALUE OF BODY MASS INDEX

Kazuhiro Matsumoto, Keishiro Fukumoto, Akira Miyajima, Masanori Hasegawa, Toshikazu Takeda, Eiji Kikuchi, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E26 - E27 2018年04月

共著,  ISSN  0022-5347

ROLES OF TOPOISOMERASE INHIBITORS AND CISPLATIN FOR CRPC IN THE POST-CABAZITAXEL SETTING

Takeo Kosaka, Hiroshi Hongo, Yota Yasumizu, Yasumasa Miyazaki, Eiji Kikuchi, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E938 - E939 2018年04月

共著,  ISSN  0022-5347

PURIFIED PROTEIN DERIVATIVE SKIN TEST PRIOR TO BACILLUS CALMETTE-GUERIN THERAPY ENHANCES THE CLINICAL EFFICACY OF BCG THERAPY IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER

Naoya Niwa, Eiji Kikuchi, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E97 - E97 2018年04月

共著,  ISSN  0022-5347

ONCOLOGIC SURVEILLANCE AFTER RADICAL NEPHROURETERECTOMY IN UPPER TRACT UROTHELIAL CARCINOMA PATIENTS: A NOVEL RISK-BASED APPROACH

Keisuke Shigeta, Eiji Kikuchi, Masayuki Hagiwara, Toshikazu Takeda, Kazuhiro Matsumoto, Takayuki Abe, Toshiaki Shinojima, Ryuichi Mizuno, Ken Nakagawa, Akira Miyajima, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E217 - E218 2018年04月

共著,  ISSN  0022-5347

MRI TUMOR CONTACT LENGTH AS A PREDICTOR OF EXTRACAPSULAR EXTENSION: OPTIMAL THRESHOLD FOR ANTERIOR AND POSTERIOR PROSTATE CANCER

Kazuhiro Matsumoto, Kimiharu Takamatsu, Seiya Hattori, Toshikazu Takeda, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （ELSEVIER SCIENCE INC）  199 （ 4 ） E901 - E901 2018年04月

共著,  ISSN  0022-5347