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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TLDR
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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Clinical significance of platelet derived growth factor-C and -D in gastric cancer
Norihito Ogawa,Mikito Inokuchi,Yoko Takagi,Hirofumi Sugita,Keiji Kato,Kazuyuki Kojima,Kenichi Sugihara +6 more
TL;DR: Findings indicate that high PDGF-D expression is strongly associated with tumor progression, recurrence, distant metastasis and poor outcomes in patients with gastric cancer, and may be an independent prognostic factor and a novel therapeutic target.
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Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer.
Takashi Kijima,Takaaki Arigami,Yoshikazu Uenosono,Tsubasa Hiraki,Shigehiro Yanagita,Daisuke Matsushita,Keishi Okubo,Masataka Shimonosono,Sumiya Ishigami,Kosei Maemura,Akihide Tanimoto,Shoji Natsugoe +11 more
TL;DR: Her2 expression can change after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer, and continuous monitoring of HER2 expression after treatments may be utilized to determine whether the continued use of trastizumab is advisable.
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Gastric Cancer: New Drugs - New Strategies.
TL;DR: The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways.
Journal ArticleDOI
In situ analysis of FGFR2 mRNA and comparison with FGFR2 gene copy number by dual-color in situ hybridization in a large cohort of gastric cancer patients.
Yasutoshi Kuboki,Christoph A. Schatz,Karl Koechert,Sabine Schubert,Janine Feng,Sabine Wittemer-Rump,Karl Ziegelbauer,Thomas Krahn,Akiko Kawano Nagatsuma,Atsushi Ochiai +9 more
TL;DR: RNAscope and DISH are suitable methods to evaluateFGFR2 status in gastric cancer and patients with very strong FGFR2 mRNA expression showed more homogeneous FGFR1 mRNA expression compared to patients with lower FGFGR2 mRNAexpression.
Journal ArticleDOI
Comprehensive pharmacogenomic characterization of gastric cancer
Jason K. Sa,Jung Yong Hong,In Kyoung Lee,Ju Sun Kim,Moon Hee Sim,Ha Jung Kim,Ji Yeong An,Tae Sung Sohn,Joon-Ho Lee,Jae Moon Bae,Sung Kim,Kyoung-Mee Kim,Seung Tae Kim,Se Hoon Park,Joon Oh Park,Ho Yeong Lim,Won Ki Kang,Nam Gu Her,Yeri Lee,Hee Jin Cho,Yong Jae Shin,Mi-Suk Kim,Harim Koo,Harim Koo,Mirinae Kim,Yun Jee Seo,Ja Yeon Kim,Min Gew Choi,Do Hyun Nam,Do Hyun Nam,Jeeyun Lee +30 more
TL;DR: The results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.
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TL;DR: The results for 20 world regions are presented, summarizing the global patterns for the eight most common cancers, and striking differences in the patterns of cancer from region to region are observed.
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New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
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Journal ArticleDOI
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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