A phase II study of bevacizumab, oxaliplatin, and docetaxel in locally advanced and metastatic gastric and gastroesophageal junction cancers

El‐Rayes, Bassel F.; Zalupski, Mark M.; Bekai-Saab, T.; Heilbrun, Lance K.; Hammad, Nazik; Patel, Bhaumik B.; Urba, Susan G.; Shields, Anthony F.; Vaishampayan, Ulka N.; Dawson, SJ; Almhanna, Khaldoun; Smith, David C.; Philip, P. A.

doi:10.1093/annonc/mdq065

Cited by 89 publications

(46 citation statements)

References 26 publications

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“…Bevacizumab in combination with 5-fluorouracilbased chemotherapy has been approved as first/second line therapy for advanced colorectal cancer (CRC) and in combination with carboplatin and/or paclitaxel has been approved as first line therapy for advanced non-small cell lung cancer (NSCLC). [18][19][20][21] The success of bevacizumab can be attributed to its sustained target inhibition resulted from its long half-life and good safety profile due to its high specificity allowing it to combine with a variety of chemotherapies. However, bevacizumab has its limitations in the clinic, such as its intravenous dosing, immunogenicity and potential to induce autoimmune diseases after long term treatment.…”

Section: Introductionmentioning

confidence: 99%

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Sun¹,

Zhou²,

Zhang³

et al. 2014

Cancer Biology & Therapy

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Section: Introductionmentioning

confidence: 99%

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Sun¹,

Zhou²,

Zhang³

et al. 2014

Cancer Biology & Therapy

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“…However, a further phase II study reported more modest efficacy in combination with oxaliplatin and docetaxel [65], comparable with the results with chemotherapy triplet regimens in phase III studies [10,11]. Unfortunately, these results reflect those reported in the international, randomized phase III AVAGAST (Avastin for Advanced Gastric Cancer) study, in which 774 patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma were randomized to a cisplatin-fluoropyrimidine doublet with bevacizumab or placebo in just 14 months.…”

Section: Clinical Data In Esophagogastric Cancer Monoclonal Antibodiementioning

confidence: 56%

Targeting Angiogenesis in Esophagogastric Adenocarcinoma

2011

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Learning Objectives After completing this course, the reader will be able to: Describe the receptors and ligands with identified roles in tumor angiogenesis and the mechanism of action of established and investigational antiangiogenic agents. Describe aspects of antiangiogenic agents that are incompletely understood and need further investigation to define their role in esophagogastric cancer. This article is available for continuing medical education credit at http://CME.TheOncologist.com The possibility of targeting tumor angiogenesis was postulated almost 40 years ago. The vascular endothelial growth factor (VEGF) family and its receptors have since been characterized and extensively studied. VEGF overexpression is a common finding in solid tumors, including esophagogastric cancer, and frequently correlates with poor prognosis. Monoclonal antibodies, soluble receptors, and small‐molecule tyrosine kinase inhibitors have been developed to inhibit tumor angiogenesis, and antiangiogenic therapy is now a component of standard treatment for advanced renal cell, hepatocellular, colorectal, breast, and non‐small cell lung carcinomas. The small‐molecule tyrosine kinase inhibitors sunitinib and sorafenib have been evaluated in phase II studies in esophagogastric cancer but appear to have only modest activity. Similarly, despite promising efficacy signals from phase II studies, the addition of the anti‐VEGF‐A monoclonal antibody bevacizumab to cisplatin plus capecitabine failed to result in a longer overall survival duration than with the chemotherapy doublet plus placebo. The response rate and progression‐free survival interval were significantly greater with bevacizumab, confirming some efficacy in advanced gastric cancer, but with inadequate benefit to justify the high cost of treatment. Evaluation of bevacizumab in the neoadjuvant and perioperative settings continues, hypothesizing that a higher response rate will translate into longer survival in patients with operable disease. Despite extensive research, the discovery of a reliable predictive biomarker for antiangiogenic therapy continues to elude the scientific and oncology communities, and mechanisms of primary and acquired resistance are incompletely understood. We are therefore currently unable to personalize antiangiogenic therapy for established indications, or use molecular selection for clinical trials evaluating novel indications.

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“…In contrast to these results, El-Rayes et al reported less efficacy of the addition of bevacizumab to the chemotherapy regimen with docetaxel and oxaliplatin in 38 previously untreated patients with locally advanced or metastatic disease [38]. The disease control rate (DCR) was 79 % with 6.6 months of PFS and 11.1 months of OS.…”

Section: Bevacizumabmentioning

confidence: 91%

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

et al. 2015

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Despite significant improvements in systemic chemotherapy during the past two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. Unfortunately, although a number of molecular targets have been studied, very few of these agents can be used in a clinical setting. In this review, we summarize the available data on anti-angiogenic agents in advanced/metastatic gastric cancer.

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A phase II study of bevacizumab, oxaliplatin, and docetaxel in locally advanced and metastatic gastric and gastroesophageal junction cancers

Abstract: The combination of bevacizumab, docetaxel, and oxaliplatin has promising activity for further evaluation in randomized trials.

Cited by 89 publications

References 26 publications

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Targeting Angiogenesis in Esophagogastric Adenocarcinoma

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

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