dc.contributor.author |
Petrylak, DP |
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dc.contributor.author |
de Wit, R |
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dc.contributor.author |
Chi, KN |
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dc.contributor.author |
Drakaki, A |
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dc.contributor.author |
Sternberg, CN |
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dc.contributor.author |
Nishiyama, H |
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dc.contributor.author |
Castellano, D |
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dc.contributor.author |
Hussain, S |
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dc.contributor.author |
Flechon, A |
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dc.contributor.author |
Bamias, A |
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dc.contributor.author |
Yu, EY |
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dc.contributor.author |
van der Heijden, MS |
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dc.contributor.author |
Matsubara, N |
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dc.contributor.author |
Alekseev, B |
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dc.contributor.author |
Necchi, A |
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dc.contributor.author |
Geczi, L |
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dc.contributor.author |
Ou, YC |
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dc.contributor.author |
Coskun, HS |
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dc.contributor.author |
Su, WP |
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dc.contributor.author |
Hegemann, M |
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dc.contributor.author |
Percent, IJ |
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dc.contributor.author |
Lee, JL |
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dc.contributor.author |
Tucci, M |
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dc.contributor.author |
Semenov, A |
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dc.contributor.author |
Laestadius, F |
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dc.contributor.author |
Peer, A |
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dc.contributor.author |
Tortora, G |
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dc.contributor.author |
Safina, S |
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dc.contributor.author |
del Muro, XG |
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dc.contributor.author |
Rodriguez-Vida, A |
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dc.contributor.author |
Cicin, I |
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dc.contributor.author |
Harputluoglu, H |
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dc.contributor.author |
Widau, RC |
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dc.contributor.author |
Liepa, AM |
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dc.contributor.author |
Walgren, RA |
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dc.contributor.author |
Hamid, O |
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dc.contributor.author |
Zimmermann, AH |
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dc.contributor.author |
Bell-McGuinn, KM |
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dc.contributor.author |
Powles, T |
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dc.date.accessioned |
2022-10-13T10:45:55Z |
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dc.date.available |
2022-10-13T10:45:55Z |
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dc.date.issued |
2017 |
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dc.identifier.uri |
http://hdl.handle.net/11616/78229 |
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dc.description.abstract |
Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. |
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dc.description.abstract |
Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m(2) plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. |
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dc.description.abstract |
Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4.07 months [95% CI 2.96-4.47] vs 2.76 months [2.60-2.96]; hazard ratio [HR] 0.757, 95% CI 0.607-0.943; p=0.0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24.5%, 95% CI 18.8-30.3) of 216 patients allocated ramucirumab and 31 (14.0%, 9.4-18.6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1-2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. |
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dc.description.abstract |
Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. |
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dc.description.abstract |
C1 [Petrylak, Daniel P.] Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. |
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dc.description.abstract |
[de Wit, Ronald] Erasmus MC Canc Inst, Rotterdam, Netherlands. |
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dc.description.abstract |
[Chi, Kim N.] British Columbia Canc Agcy, Vancouver, BC, Canada. |
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dc.description.abstract |
[Drakaki, Alexandra] UCLA, David Geffen Sch Med, Los Angeles, CA 90095 USA. |
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dc.description.abstract |
[Sternberg, Cora N.] San Camillo & Forlanini Hosp, Rome, Italy. |
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dc.description.abstract |
[Nishiyama, Hiroyuki] Univ Tsukuba, Tsukuba, Ibaraki, Japan. |
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dc.description.abstract |
[Castellano, Daniel] Hosp Univ 12 Octubre CiberOnc, Madrid, Spain. |
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dc.description.abstract |
[Hussain, Syed] Plymouth Univ, Peninsula Sch Med & Dent, Plymouth, Devon, England. |
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dc.description.abstract |
[Flechon, Aude] Ctr Leon Berard, Lyon, France. |
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dc.description.abstract |
[Bamias, Aristotelis] Univ Athens, Athens, Greece. |
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dc.description.abstract |
[Yu, Evan Y.] Univ Washington, Seattle, WA 98195 USA. |
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dc.description.abstract |
[van der Heijden, Michiel S.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. |
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dc.description.abstract |
[Matsubara, Nobuaki] Hosp East, Natl Canc Ctr, Chiba, Japan. |
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dc.description.abstract |
[Alekseev, Boris] PA Herzen Moscow Oncol Res Inst, Moscow, Russia. |
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dc.description.abstract |
[Necchi, Andrea] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. |
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dc.description.abstract |
[Geczi, Lajos] Natl Inst Oncol, Budapest, Hungary. |
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dc.description.abstract |
[Ou, Yen-Chuan] Taichung Vet Gen Hosp, Taichung, Taiwan. |
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dc.description.abstract |
[Coskun, Hasan Senol] Akdeniz Univ, Sch Med, Antalya, Turkey. |
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dc.description.abstract |
[Su, Wen-Pin] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan, Taiwan. |
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dc.description.abstract |
[Su, Wen-Pin] Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med, Tainan, Taiwan. |
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dc.description.abstract |
[Hegemann, Miriam] Univ Hosp, Tubingen, Germany. |
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dc.description.abstract |
[Percent, Ivor J.] Florida Canc Specialists, Port Charlotte, FL USA. |
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dc.description.abstract |
[Lee, Jae-Lyun] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. |
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dc.description.abstract |
[Tucci, Marcello] Univ Turin, San Luigi Gonzaga Hosp, Dept Oncol, Div Med Oncol, Turin, Italy. |
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dc.description.abstract |
[Semenov, Andrey] RBHI Ivanovo Reg Oncol Dispensary, Ivanovo, Russia. |
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dc.description.abstract |
[Laestadius, Fredrik] Ctr Oscar Lambret, Lille, France. |
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dc.description.abstract |
[Peer, Avivit] Rambam Hlth Care Campus, Haifa, Israel. |
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dc.description.abstract |
[Tortora, Giampaolo] Univ Verona, Verona, Italy. |
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dc.description.abstract |
[Tortora, Giampaolo] Azienda Osped Univ Integrata, Verona, Italy. |
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dc.description.abstract |
[Safina, Sufia] Tatarstan Reg Canc Ctr, Kazan, Russia. |
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dc.description.abstract |
[Garcia del Muro, Xavier] Univ Barcelona, IDIBELL, Inst Catala Oncol Hosp, Barcelona, Spain. |
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dc.description.abstract |
[Rodriguez-Vida, Alejo] Hosp Mar, Barcelona, Spain. |
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dc.description.abstract |
[Cicin, Irfan] Trakya Univ, Edirne, Turkey. |
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dc.description.abstract |
[Harputluoglu, Hakan] Inonu Univ, Malatya, Turkey. |
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dc.description.abstract |
[Widau, Ryan C.; Liepa, Astra M.; Walgren, Richard A.; Hamid, Oday; Zimmermann, Annamaria H.; Bell-McGuinn, Katherine M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. |
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dc.description.abstract |
[Powles, Thomas] Queen Mary Univ London, Barts Canc Inst, London, England. |
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dc.source |
LANCET |
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dc.title |
Ramucirumab plus docetaxel versus placebo plus docetaxel in patients |
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dc.title |
with locally advanced or metastatic urothelial carcinoma after |
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dc.title |
platinum-based therapy (RANGE): a randomised, double-blind, phase 3 |
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dc.title |
trial |
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