Cetuximab plus cisplatin–5-fluorouracil versus cisplatin–5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie

Lorenzen, Sylvie; Schuster, Tibor; Porschen, Rainer; Al-Batran, S.; Hofheinz, Ralf; Thuss‐Patience, Peter; Moehler, Markus; Grabowski, Patricia; Arnold, Dirk; Greten, Tim F.; Müller, L.; Röthling, N.; Peschel, C; Langer, Rupert; Lordick, Florian

doi:10.1093/annonc/mdp069

Cited by 216 publications

(179 citation statements)

References 26 publications

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“…It has been reported that compared with chemotherapy alone, cetuximab plus chemotherapy could more obviously improve the curative effect for metastatic SCCO (Lorenzen et al, 2009). Because the number of cases in this Meta analysis is still insufficient, conclusions were inconsistent with the previously one, it still need to continue to accumulate clinical pathological data, observe prognosis, and do a more comprehensive and further study on EGFR over-expression correlates with SCCO, so as to provide a more sufficient theoretical basis for anti-EGFR target therapy in SCCO.…”

Section: Discussionmentioning

confidence: 99%

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Wang

Yu²,

Jing³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.

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Section: Discussionmentioning

confidence: 99%

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Wang

Yu²,

Jing³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Cetuximab combined with radiotherapy is approved for treatment of primary SCC of the oropharynx, hypopharynx, or larynx, and cetuximab combined with platinum is approved for treatment of recurrent or metastatic SCC of the oropharynx, hypopharynx, larynx, and oral cavity, based on positive clinical trials (12,13). Cetuximab has been tested in combination with irinotecan, cisplatin, and concurrent radiotherapy in esophageal cancer in multiple phase II studies (14)(15)(16)(17). The results are mixed regarding safety and question the efficacy of including cetuximab in treatment.…”

Section: Introductionmentioning

confidence: 99%

Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures

Kjær

Lindsted

Fröhlich

et al. 2016

Molecular Cancer Therapeutics

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Squamous cell carcinomas (SCC) arising in upper parts of the aerodigestive tract are among the leading causes of death worldwide. EGFR has been found to play an essential role in driving the malignancy of SCC of the upper aerodigestive tract (SCCUAT), but, despite this, clinical results using a range of different EGFR-targeted agents have been disappointing. Cetuximab is currently the only EGFR-targeted agent approved by the FDA for treatment of SCCUAT. However, intrinsic and acquired cetuximab resistance is a major problem for effective therapy. Thus, a better understanding of the mechanisms responsible for cetuximab resistance is valuable for development of the next generation of antibody therapeutics. In order to better understand the underlying mechanisms of cetuximab resistance in SCCUAT, we established from cetuximab-sensitive models cell lines with acquired resistance to cetuximab by continuous selective pressure in vitro and in vivo. Our results show that resistant clones maintain partial dependency on EGFR and that receptor tyrosine kinase plasticity mediated by HER3 and IGF1R plays an essential role. A multitarget mAb mixture against EGFR, HER3, and IGF1R was able to overcome cetuximab resistance in vitro. To our surprise, these findings could be extended to include SCCUAT cell lines with intrinsic resistance to cetuximab, suggesting that the triad consisting of EGFR, HER3, and IGF1R plays a key role in SCCUAT. Our results thus provide a rationale for simultaneous targeting of EGFR, HER3, and IGF1R in SCCUAT. Mol Cancer Ther; 15(7); 1614-26. Ó2016 AACR.

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“…In contrast, our own search yielded a total of 6777 records of which 45 [3][4][5] were RCTs. Of the 37 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]19,20,[22][23][24][25][26][27][28][30][31][32][33][34][36][37][38]40,41,43,45,47,48 trials of cetuximab, 32 [3][4][5][6][8][9][10][11][12][14][15][16]…”

Section: Search Strategy and Missing Trialsmentioning

confidence: 99%

Letter to the editor

Sterrantino

Miroddi

Phillips

et al. 2016

Intl Journal of Cancer

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Dear Editor, We are writing to bring serious concerns about the validity of the article "Hematologic toxicity assessment in solid tumor patients treated with cetuximab: A pooled analysis of 18 randomized controlled trials" 1 authored by Ran Cui et al. and recently published by the International Journal of Cancer to your attention. After careful reading, we firmly believe that the review uses inappropriate methods and incorrect data, and therefore that the conclusions are misleading.We should be clear that the reason that we have been able to consider the data so carefully is that our group is conducting a systematic review on serious thromboembolic adverse events which has a very similar design (PROSPERO registration number CRD42014009165 2 ), although our systematic review also includes randomized controlled trials (RCTs), in which panitumumab (another approved anti-EGFR monoclonal antibody) is tested as an add-on to standard regimens.We detail the many shortcomings of the research reported by Cui et al. below. Search Strategy and Missing TrialsWe were surprised by the small number of records (511) returned by the authors' initial search, the number of RCTS identified (18) and by the small number of articles that were excluded on grounds of lack of data (2). In contrast, our own search yielded a total of 6777 records of which 45 3-5,7-48 were RCTs. Of the 37 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]19,20,[22][23][24][25][26][27][28][30][31][32][33][34][36][37][38]40,41,43,45,47,48 trials of cetuximab, 32 [3][4][5][6][8][9][10][11][12][14][15][16]19,20,[22][23][24][25][26][27][28][30][31][32][33][34][36][37][38]40,41,43,45,47,48 reported data on hematologic toxicities.Cui et al. do not report their search strategies in full, making it difficult to have confidence in their quality. From the information given, it would seem that although there are several rigorous search filters that can be used to identify RCTs, none of these were used in either MEDLINE or Embase. It also seems that the Cochrane Central Register of Controlled Trials was not used. The impact of these choices would be to restrict the number of articles identified by the literature searching.As of October 31, 2013, the time at which the literature search by Cui et al. was done, 6 of the additional 16 RCTs that we identified were already published. These 6 trials (including over 1,700 participants) should therefore have been identified and added to the 18 trials that they included (Table 1).To date, further data from >5,000 patients are available, as compared to the analysis of Cui et al.; around one-third of these data were already published at the time of their search, and therefore have been missed from the review.

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Cetuximab plus cisplatin–5-fluorouracil versus cisplatin–5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie

Abstract: Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.

Cited by 216 publications

References 26 publications

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures

Letter to the editor

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