Phase II Trial of Erlotinib in Gastroesophageal Junction and Gastric Adenocarcinomas: SWOG 0127

Dragovich, Tomislav; McCoy, Sarah Westcott; Fenoglio‐Preiser, Cecilia M.; Wang, Jiang; Benedetti, Jacqueline; Baker, Amanda F.; Hackett, Christopher B.; Urba, Susan G.; Zaner, Ken S.; Blanke, Charles D.; Abbruzzese, James L.

doi:10.1200/jco.2006.07.1316

Cited by 288 publications

(178 citation statements)

References 22 publications

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“…A number of strategies against EGFR and HER-2 have been developed, including mAbs and smallmolecule kinase inhibitors (Mendelsohn and Baselga, 2003). There have been data from clinical trials demonstrating the results of applying anti-EGFR tyrosine kinase inhibitors (gefitinib or erlotinib) to oesophageal adenocarcinoma (Dragovich et al, 2006;Kwak et al, 2006), indicating that erlotinib may be active in patients with oesophageal adenocarcinoma and the useful molecular marker will be needed to predict the therapeutic response.…”

Section: Discussionmentioning

confidence: 99%

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

et al. 2007

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We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n ¼ 66) detected by immunohistochemistry and (b) cetuximab-and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the 51 Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR-and HER-2 expression. Out of both EGFR-and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.

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Section: Discussionmentioning

confidence: 99%

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

et al. 2007

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“…Preliminary results from phase I/II studies of erlotinib plus FOLFOX or XELOX (Xeloda plus oxaliplatin) in advanced refractory colorectal cancer suggest that the addition of erlotinib to standard chemotherapy has some beneficial effects (123)(124)(125). Erlotinib has shown modest efficacy in patients with esophageal or gastroesophageal junction cancer, with response rates of 9% to 15%, but has shown no activity in patients with gastric cancer (126,127). A phase II trial of erlotinib in patients with unresectable hepatocellular carcinoma showed that 25% of patients remained progression-free at 4 months (128).…”

Section: Egfr Inhibitionmentioning

confidence: 99%

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

Tabernero

2007

Molecular Cancer Research

380

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“…Anticancer drugs aimed at molecular regulators, including epidermal growth factor receptor (EGFR or HER1), its homologue c-erb-2 (HER2), have been developed and shown to be effective in the breast, lung, and colon cancers (Slamon et al, 2001;Thatcher et al, 2005;Gatzemeier et al, 2007;Sobrero et al, 2008). These drugs have been evaluated in advanced gastric cancer, but two EGFR tyrosine kinase inhibitors were found to be ineffective (Dragovich et al, 2006;Rojo et al, 2006).…”

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confidence: 99%

Relation between outcomes and localisation of p-mTOR expression in gastric cancer

et al. 2009

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The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2 -4, P ¼ 0.003), involved lymph nodes (P ¼ 0.010), and tumour stage (I vs II -IV, P ¼ 0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (Po0.001, ¼ 0.035, and o0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P ¼ 0.037) and overall survival (OS, P ¼ 0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P ¼ 0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.

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Phase II Trial of Erlotinib in Gastroesophageal Junction and Gastric Adenocarcinomas: SWOG 0127

Abstract: Erlotinib is active in patients with GEJ adenocarcinomas, but appears inactive in gastric cancers. The molecular correlates examined were not predictive of the patient therapeutic response.

Cited by 288 publications

References 22 publications

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

Relation between outcomes and localisation of p-mTOR expression in gastric cancer

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