A Phase II Study of the c-Met Inhibitor Tivantinib in Combination with FOLFOX for the Treatment of Patients with Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction, or Stomach

Pant, Shubham; Patel, Manish R.; Kurkjian, Carla; Hemphill, Brian; Flores, Maria Regina C.; Thompson, Dana S.; Bendell, Johanna C.

doi:10.1080/07357907.2017.1337782

Cited by 28 publications

(18 citation statements)

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“… 3 , 4 It has been reported that TNM stage, lymph node involvement, and metastasis were the putative standards for surgical options and prognosis prediction of GC patients. 5 , 6 In recent studies, molecular profiling has contributed to our understanding of the progression and potential targets of multiple human cancers. Molecular biomarkers are not only used for diagnosis but also act as potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

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miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R

Liu¹,

Yang

Wang³

2018

OTT

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BackgroundIn recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC.Materials and methodsWe analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients. Furthermore, in vitro and in vivo assays were used to investigate the molecular mechanisms of miR-598 and IGF-1R.ResultsmiR-598 expression was frequently downregulated in GC tissues and cells, and significantly correlated with poor prognosis, vascular invasion, TNM stage, and lymph node metastases as well as IGF-1R expression. The overexpression of miR-598 obviously inhibited cell proliferation, migration, invasion, and induced cell cycle arrest in the G1/S phase, and increased the apoptosis of GC cells. The overexpression of miR-598 also significantly inhibited ERK1/2 and Akt phosphorylation level. In vivo assay validated the inhibitory effect of miR-598 on tumor growth. Further studies showed that miR-598 inhibited IGF-1R protein expression by directly targeting its 3′-UTR. Besides, over-expression of IGF-1R reversed the inhibitory effects of miR-598, while suppression of IGF-1R expression showed inverse effects.ConclusionmiR-598 suppresses GC cell proliferation, migration and invasion by directly targeting IGF-1R expression. Thus, miR-598 may be a useful target for GC patients.

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Section: Discussionmentioning

confidence: 99%

“…In addition, malignant or advanced GC is characterized as malignant proliferation, vascular invasion, and lymphatic metastasis. 5 , 6 Thus, it is essential to investigate novel targets to effectively treat GC patients.…”

Section: Introductionmentioning

confidence: 99%

miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R

Liu¹,

Yang

Wang³

2018

OTT

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“…Patients with high c-MET expression had inferior PFS and OS, proving the correlation of c-MET expression with poorer outcomes. 83 Another ongoing Phase I-II trial is testing the combination of AMG-337 with mFOLFOX6 in c-MET-positive advanced-stage GC patients. 84 Volitinib was also tested in combination with docetaxel, and results showed good tolerance and superior anti-tumor efficacy than either agent alone.…”

Section: Combination With Chemotherapymentioning

confidence: 99%

<p><em>MET</em> Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential?</p>

Darsa¹,

Sayed²,

Abdel‐Rahman³

2020

JEP

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Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer prognosis. Tyrosine kinase inhibitors targeting the HGF/MET pathway were studied in MET-positive gastric cancer, but no substantial benefit was proven. Some patients responded in early phase trials but later developed resistance. Others failed to show any benefit at all. Etiologies of resistance may entail inappropriate patient selection with a lack of MET detection standardization, tumor alternative pathways, variable MET amplification, and genetic variation. Optimizing MET detection techniques and better understanding the MET pathway, as well as tumor bypass mechanisms, are an absolute need to devise means to overcome resistance using targeted therapy alone, or in combination with other synergistic agents to improve outcomes of patients with MET-positive GC.

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“…Hastalar, Dünya Sağlık Örgütü'nün yaşlılık tanımı ve literatürdeki önceki çalımalar göz önüne alınarak, 65 yaş sınır kabul edilerek iki gruba ayrıldı (20)(21)(22).…”

Section: Yöntemlerunclassified

Prognostic Effect of Peritoneal Metastasis in Patients with Metastatic Gastric Carcinoma

Demi̇rci¹

2017

JAREM

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ÖZAmaç: Metastatik mide karsinomlu hastalarda periton metastazı varlığının prognozla ilişkisini göstermeyi amaçladık.Yöntemler: Ocak 2005 -Ağustos 2014 tarihleri arasında metastatik mide adenokarsinomu tanısı alan, 87 hasta retrospektif olarak tarandı. Periton metastazı varlığının genel sağ kalım ve progresyonsuz sağ kalım ile ilişkisi incelendi. Periton metastazı varlığının diğer klinikopatolojik özelliklerle korelasyonu araştırıldı.Bulgular: Tek değişkenli analizde ECOG (Eastern Cooperative Oncology Group) performans durumu 0-1 olan (p=0,04), histopatolojik olarak müsinöz komponent içermeyen (p=0,043) ve periton metastazı olmayan hastaların (p=0,026) genel sağ kalımı istatistiksel olarak anlamlı daha iyiydi. Çok değişkenli analizde, periton metastazı olan hastalar (HR,1,681; %95CI, 1,032-2,739; p=0,037) daha kötü genel sağ kalıma sahipti. Progresyonsuz sağ kalım, ECOG performans durumu ≥2 olan hastalarda hem tek değişkenli (8,1 ay -5,5 ay, p=0,001) hem de çok değişkenli (HR,2,228; %95CI,1,553; p=0,001) analizde anlamlı olarak daha kötüydü.Sonuç: Periton metastatik mide karsinomlu hastalar, periton metastazı olmayan hastalarla kıyaslandığında, istatistiksel olarak anlamlı daha kötü genel sağ kalım süresine sahiptir. (JAREM 2017; 7) Anahtar Kelimeler: Metastatik mide kanseri, periton metastazı, prognoz ABSTRACT Objective: The aim of this study is to evaluate of prognosis of the patients with peritoneal carcinomatosis in metastatic gastric carcinoma.Methods: Eighty-seven patients diagnosed with metastatic gastric adenocarcinoma between January 2005 and August 2014 were retrospectively reviewed. The effect of peritoneal metastasis on overall survival and progression-free survival was assessed.Results: In univariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (p=0.04), histologic type (p=0.04) and site of metastasis (p=0.02) were significant prognostic factors for overall survival; favoring ECOG performance status 0-1, histopathologically without mucinous component, patients without peritoneal metastasis respectively. Patients with peritoneal metastasis (HR, 1.681; 95% CI, 1.032-2.739; p=0.037) had worse overall survival in multivariate analysis. ECOG PS≥2 predicted inferior PFS in both univariate (8.1months versus 5.5 months, p=0.001) and multivariate analysis (HR, 2.228; 95% CI, 1.397-3.553; p=0.001). Conclusion:The presence of peritoneal metastasis in patients with metastatic gastric carcinoma is associated with significantly shorter overall survival compared to patients without peritoneal metastasis. (JAREM 2017; 7) Keywords: Metastatic gastric cancer, peritoneal metastasis, prognosis GİRİŞMide karsinomu, dünya çapında en sık tanı konulan dördüncü ve kansere bağlı ölümlerin ise en sık ikinci nedenidir (1). Tüm gastrointestinal kanserler arasında en sık görülenlerden biri olup, oldukça kötü bir prognoza sahiptir (2, 3). Gastrektomi, halen tek küratif tedavi seçeneğidir. Operasyona rağmen hastaların %40-60'ında hastalık tekrarı görülmektedir (4). Bunun yanı sıra mide karsinomları...

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A Phase II Study of the c-Met Inhibitor Tivantinib in Combination with FOLFOX for the Treatment of Patients with Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction, or Stomach

Abstract: The combination treatment of tivantinib plus FOLFOX in patients with advanced GE cancer showed a response and PFS in the range of historical controls for first-line FOLFOX therapy. However, two patients had extended time on study treatment (36 and 45 cycles) at the time of data cutoff.

Cited by 28 publications

References 24 publications

miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R

miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R

<p><em>MET</em> Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential?</p>

Prognostic Effect of Peritoneal Metastasis in Patients with Metastatic Gastric Carcinoma

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