Journal ArticleDOI
Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial
Florian Lordick,Yoon-Koo Kang,Hyun Cheol Chung,Pamela Salman,Sang Cheul Oh,György Bodoky,G. Kurteva,Constantin Volovat,Vladimir Moiseyenko,Vera Gorbunova,Joon Oh Park,Akira Sawaki,Ilhan Celik,Heiko Götte,Helena Melezínková,Markus Moehler +15 more
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Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in the EXPAND trial.Abstract:
Summary Background Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m 2 (on days 1–14) and intravenous cisplatin 80 mg/m 2 (on day 1), with or without weekly cetuximab (400 mg/m 2 initial infusion on day 1 followed by 250 mg/m 2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2–5·5) compared with 5·6 months (5·1–5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92–1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3–4 adverse events, including grade 3–4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3–4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3–4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding Merck KGaA.read more
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Perioperative chemotherapy with or without epidermal growth factor receptor blockade in unselected patients with locally advanced oesophagogastric adenocarcinoma: Randomized phase II study with advanced biomarker program of the German Cancer Society (AIO/CAO STO-0801).
Michael Stahl,Annett Maderer,Florian Lordick,André L. Mihaljevic,Stefan Kanzler,Thomas Hoehler,Peter C. Thuss-Patience,Stefan Mönig,Volker Kunzmann,Sebastian Schroll,Andreas Sandermann,Andrea Tannapfel,Hans-Joachim Meyer,Christoph Schuhmacher,Hansjochen Wilke,Markus Moehler,Arbeitsgemeinschaft Internistische Onkologie (Aio) Oesophageal +16 more
TL;DR: Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy, and the addition of panitumumab to ECX did not improve downstaging of locally advanced EGC.
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Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer
TL;DR: A review of Phase II-III studies published or referenced in major oncology congress publications from 1970 to 2013 was performed, finding no comparative studies of the same regimens with or without anthacyclines; thus, the effectiveness of anthacyClines remains under debate.
Journal ArticleDOI
Regional differences in advanced gastric cancer: exploratory analyses of the AVAGAST placebo arm.
Akira Sawaki,Yasuhide Yamada,Kensei Yamaguchi,Tomohiro Nishina,Toshihiko Doi,Taroh Satoh,Taroh Satoh,Keisho Chin,Narikazu Boku,Yasushi Omuro,Yoshito Komatsu,Yasuo Hamamoto,Wasaburo Koizumi,Shigehira Saji,Shigehira Saji,Manish A. Shah,Eric Van Cutsem,Yoon-Koo Kang,Junko Iwasaki,Hiroshi Kuriki,Wataru Ohtsuka,Atsushi Ohtsu +21 more
TL;DR: Regional differences in the healthcare environment may have contributed to the differences in overall survival observed in the AVAGAST study.
Journal ArticleDOI
A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?
Domenico Ciliberto,Nicoletta Staropoli,F. Caglioti,Simona Gualtieri,Lucia Fiorillo,Silvia Chiellino,Antonina Maria De Angelis,Francesco Mendicino,Cirino Botta,Michele Caraglia,Pierfrancesco Tassone,Pierosandro Tagliaferri +11 more
TL;DR: A systematic review and meta-analyses on each relevant targeted-pathway demonstrated a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
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Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Yung-Jue Bang,Eric Van Cutsem,A. Feyereislova,Hyun Cheol Chung,Lin Shen,Akira Sawaki,Florian Lordick,Atsushi Ohtsu,Yasushi Omuro,Taroh Satoh,G. Aprile,Evgeny Kulikov,Julie Hill,Michaela Lehle,Josef Rüschoff,Yoon-Koo Kang +15 more
TL;DR: Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.
Journal ArticleDOI
Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer
Jan B. Vermorken,Ricard Mesia,Fernando Rivera,Eva Remenar,Andrzej Kawecki,Sylvie Rottey,Jozsef Erfan,Dmytro Zabolotnyy,Heinz Roland Kienzer,Didier Cupissol,Frederic Peyrade,Marco Benasso,Ihor Vynnychenko,Dominique De Raucourt,Carsten Bokemeyer,Armin Schueler,Nadia Amellal,Ricardo Hitt +17 more
TL;DR: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracils) significantly prolonged the median overall survival and improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
Journal ArticleDOI
Capecitabine and oxaliplatin for advanced esophagogastric cancer.
TL;DR: Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer, in a two-by-two design.
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