A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus

Gastrointestinal Oncology Service/Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer (Impact Factor: 4.89). 04/2011; 117(7):1409-14. DOI: 10.1002/cncr.25602
Source: PubMed


Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have activity in solid tumors. The authors evaluated an oral EGFR TKI, erlotinib, in patients with previously treated esophageal cancer.
Thirty patients with measurable, metastatic cancer of the esophageal and gastroesophageal junction received 150 mg erlotinib daily. EGFR-negative tumors (6 patients; 20%) and EGFR-over expressing tumors (24 patients; 80%) were treated. Most patients were men (70%) with adenocarcinoma (57%) and had received previous chemotherapy (97%).
Two partial responses were observe d in the EGFR-positive cohort (2 of 24 patients; 8%), and no responses were observed in the EGFR-negative cohort (0 of 6 patients). Reponses were limited to patients who had squamous cell carcinoma (2 of 13 patients; 15%; response duration, 5.5-7 months). The time to tumor progression was longer in patients who had squamous cell carcinoma (3.3 months; range, 1-24 months) compared with patients who had adenocarcinoma (1.6 months; range, 1-6 months; P = .026). Therapy was tolerable with the expected toxicity of skin rash (grade 1-2, 67%; grade 3, 10%).
Erlotinib had limited activity in patients with esophageal cancer, and responses and some protracted stable disease were observed in those with squamous cell carcinoma. Efficacy according to EGFR status could not be assessed given the rarity of EGFR-negative tumors. The current results indicated that further evaluation of this agent in squamous cell carcinoma is warranted. Cancer 2011. © 2010 American Cancer Society.

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Available from: Manish A Shah, Feb 28, 2015
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    • "HER2 (ERBB2) overexpression varied according to gastric cancer subtypes and targeting HER2 through the use of a humanized monoclonal antibody Trastuzumab (Herceptin) has been very successful in the treatment of HER2-overexpressed gastric cancers [31]. Overexpression of EGFR is associated with gastric cancer and there are several drugs such as Gefitinib, Erlotinib, and Ceutuximab that target EGFR mutations either in combination or as single agents [32]–[35]. High VEGF levels in the serum is associated with the prognosis of advanced gastric cancer; bevacizumab, an anti-VEGF monoclonal antibody, helps enhance survival rate of these patients [36], [37]. PI3K/mTOR pathway activation has been demonstrated in gastric cancer [38] and everolimus (Afinitor) has shown some significant response in the gastric cancer patients through targeting the mutations associated with PI3K/mTOR pathway [39], [40]. "
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    PLoS ONE 07/2014; 9(7):e100442. DOI:10.1371/journal.pone.0100442 · 3.23 Impact Factor
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    • "As is known, overexpression of EGFR and HER2 has been observed in over 30% of esophageal carcinomas, and their overexpression is correlated with reduced survival, increased risk of recurrence, distant metastasis, and resistance to radiotherapy [18]. Therefore, the effects of some monospecific antibodies and tyrosine kinase inhibitors that block EGFR or HER2 function, such as cetuximab, trastuzumab, gefitinib, and erlotinib on esophageal carcinoma have been examined, but the efficacy is limited so far [19]–[22]. Different from monoclonal antibodies and tyrosine kinase inhibitors, immunotoxins are considered to be highly effective on cancer therapy with the advantage of the specificity of antibodies or ligands and the cytotoxicity of toxins [23]. "
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    PLoS ONE 03/2014; 9(3):e92986. DOI:10.1371/journal.pone.0092986 · 3.23 Impact Factor
    • "The addition of bevacizumab and erlotinib to neoadjuvant concurrent chemoradiation therapy for localized esophageal/gastroesophagel cancer did not demonstrate survival benefit but targeted agent specific toxicities were evident.[37] Erlotinib monotherapy when studied as a second line agent in a phase II trial in metastatic esophageal cancer, showed some benefit in squamous cell tumors but not in adenocarcinoma (3.3 mo vs. 1.6 mo, P = 0.026).[38] A phase II trial (SWOG 0127) evaluated erlotinib as a monotherapy in unresectable/metastatic gastroesophagel junction and gastric adenocarcinoma and found its activity in gastroesophageal junction tumors but not in gastric adenocarcinoma.[39] "
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