Trastuzumab, Paclitaxel, Cisplatin, and Radiation for Adenocarcinoma of the Esophagus: A Phase I Study #

Safran, Howard; DiPetrillo, Thomas A.; Nadeem, Ahmed; Steinhoff, Margaret M.; Tantravahi, Umadevi; Rathore, Ritesh; Wanebo, Harold J.; Hughes, M. A.; Maia, C.; Tsai, James; Pasquariello, Terry; Pepperell, John R.; Cioffi, William G.; Kennedy, T. A.; Reeder, Laurie B.; Ng, Tony; Adrian, Alyn; Goldstein, Lisa; Chak, Bapsi; Choy, Hak

doi:10.1081/cnv-200032951

Cited by 50 publications

(35 citation statements)

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“…30,31 However, the FDA and Health Canada approvals for trastuzumab (Herceptin r ) treatment include all types of oesophagogastric adenocarcinomas; therefore, strict criteria for ErbB2 assessment in oesophageal adenocarcinomas are of the highest clinical relevance for selecting patients for ErbB2-targeted treatment, which may represent an expensive but promising additional therapeutic option for the advanced stages of this disease. [32][33][34][35][36] In summary, in this study, we found that a significant number of oesophageal adenocarcinomas are positive for ErbB2. The assessment of ErbB2 by immunohistochemistry in combination with in situ hybridisation (bright field double in situ hybridisation or fluorescence in situ hybridisation) reveals highly relevant prognostic information and may also serve as a basis for targeted trastuzumab therapy.…”

Section: Discussionmentioning

confidence: 80%

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

et al. 2011

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Amplification and overexpression of ErbB2 (Her2) is a frequent event in oesophageal adenocarcinomas. Assessment of ErbB2 status is crucial for identifying patients who are likely to benefit from treatment with trastuzumab. In this study, we performed a comprehensive analysis of ErbB2 amplification and expression in 142 oesophageal adenocarcinomas by comparing the most commonly used methods for ErbB2 assessment: ErbB2 expression was determined by immunohistochemistry and was scored (0, 1 þ , 2 þ and 3 þ ) according to a recently described modified scoring system for gastric cancer. ErbB2 amplification was evaluated by bright field double in situ hybridisation. The results were compared with pathologic features, patients' survival and previously published data from fluorescence in situ hybridisation analysis. On the basis of immunohistochemistry, which was applicable in 110 cores of the cases, 83 tumours (75%) had a score of 0 or 1 þ (immunohistochemistry negative), 13 tumours (12%) were scored as 2 þ and 14 tumours (13%) were scored as 3 þ . In situ hybridisation data were obtained from 142 cases. There was a highly significant correlation of immunohistochemistry, bright field in situ hybridisation and fluorescent in situ hybridisation (Po0.001 each). In total, 41 tumours (29%) were categorised as ErbB2 positive, which was defined as immunohistochemistry 3 þ and/or an ErbB2/Chr17 quotient of Z2 as assessed by either bright field double in situ hybridisation or fluorescence in situ hybridisation. ErbB2 positivity was observed more frequently in tumours with lower differentiation grades (P ¼ 0.029). Patients with ErbB2-positive tumours had a significantly worse prognosis, both in univariate analysis (P ¼ 0.004) and in multivariate analysis (P ¼ 0.03).In conclusion, we demonstrate that a significant number of oesophageal adenocarcinomas are positive for ErbB2. Assessment of ErbB2 amplification can be equivalently performed by conventional fluorescence in situ hybridisation or other lightmicroscopy-based methods, such as the novel bright field double in situ hybridisation technique. Modern Pathology (2011) 24, 908-916;

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Section: Discussionmentioning

confidence: 80%

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

et al. 2011

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“…Although many responders were reported, the possible contribution of Herceptin s cannot be appreciated in this study. 34 Clinical trials or individual case studies investigating the response of HER-2 amplified metastatic esophageal cancers to Herceptin s are clearly needed.…”

Section: Discussionmentioning

confidence: 99%

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

et al. 2007

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HER-2 is the target for antibody based treatment of breast cancer (Herceptin s ). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTestt; DAKO) and fluorescence in situ hybridization (FISH; PathVysiont; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (Po0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high-level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptin s should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin s .

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“…Trastuzumab or other HER2 related medication on treatment of HER2 amplification esophageal adenocarcinoma: Safran et al [70,71] …”

Section: Her2 Amplification or Overexpression Correlating With Patienmentioning

confidence: 99%

HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment

Zhou¹,

Hick²

2013

Oncogene and Cancer - From Bench to Clinic

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Trastuzumab, Paclitaxel, Cisplatin, and Radiation for Adenocarcinoma of the Esophagus: A Phase I Study #

Abstract: HER-2/neu is overexpressed in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be added at full dose to cisplatin, paclitaxel, and radiation. Future studies of trastuzumab in esophageal adenocarcinoma are indicated.

Cited by 50 publications

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Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment

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