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A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients

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A Correction to this article was published on 14 December 2017

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Abstract

Background

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate.

Objective

We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study.

Patients and Methods

Between November 2006 and April 2009, 50 patients with stage II–IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients.

Results

Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7–22.8). Median overall survival was 23.4 months (95% CI 12.2–36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1–11.6). The toxicity profile was acceptable.

Conclusions

Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature.

Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

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Change history

  • 14 December 2017

    Errors were subsequently identified in the article and the following corrections should be noted

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Acknowledgements

The physicians listed below cared for the patients in this study. The authors thank them for their cooperation and support:

Study Chairs: J.M. Tabernero and J. Giralt (Vall d’Hebron University Hospital, Barcelona),

F. Rivera and C. López (H. U. Marqués Valdecilla, Santander), B. Navalpotro (Vall d’Hebron University Hospital, Barcelona), M. Galán and A. Boladeras (ICO Hospitalet, Barcelona), R. López and A. Gómez (C.H. Universitario de Santiago, Santiago de Compostela), P. García and F. Calvo (H. Gregorio Marañón, Madrid), J E. Alés-Martínez and R. García-Alejo (H. ruber Internacional, Madrid), B. Queralt and E. Canals (H. Josep Trueta [ICO], Girona), A. Antón and M. Tejedor (H. Miguel Servet, Zaragoza), A. Hervás (H. Ramón y Cajal, Madrid), C. Grávalos and Mª A. Pérez de Escutia (H. 12 de Octubre, Madrid), and A. Palacios and E. Aranda (Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network [RTICC], Instituto de Salud Carlos III, Spain).

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): Susana Rodriguez.

Monitoring, Statistics and Data Management: TFS Trial Form Support Spain Mar Nicolau y Marta Muñoz.

Author information

Authors and Affiliations

  1. Vall d’Hebron University Hospital, Department of Medical Oncology, and Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron, 119-129, Barcelona, Spain

    Maria Alsina, Francisco Javier Ramos & Josep Tabernero

  2. Department of Medical Oncology, H.U. Marqués Valdecilla, Av. Valdecilla, 25, Santander, Spain

    Fernando Rivera & Carlos López

  3. Department of Medical Oncology, ICO Hospitalet, Avinguda de la Granvia, 199-203, Barcelona, Spain

    Maica Galán

  4. Medical Oncology Department and Translational Medical Oncology Group, University Clinical Hospital and Health Research Institute (IDIS); CIBERONC, Santiago de Compostela University School of Medicine, Santiago de Compostela, Spain

    Rafael López

  5. Department of Medical Oncology, H. Gregorio Marañón, Calle del Dr. Esquerdo, 46, Madrid, Spain

    Pilar García-Alfonso

  6. Department of Medical Oncology, H. Ruber Internacional, Calle de la Masó, 38, Madrid, Spain

    José Enrique Alés-Martinez

  7. Spain and H Nuestra Sra Sonsoles, C/ Avda. Juan Carlos I, Avila, Spain

    José Enrique Alés-Martinez

  8. Department of Medical Oncology, H. JosepTrueta (ICO), Avinguda de França, Girona, Spain

    Bernardo Queralt

  9. Department of Medical Oncology, H. Miguel Servet, Paseo Isabel la Católica, 1-3, Zaragoza, Spain

    Antonio Antón

  10. Department of Medical Oncology, H. Ramón y Cajal, Ctra. Colmenar Viejo, km. 9, 100, Madrid, Spain

    Alfredo Carrato

  11. Department of Medical Oncology, H. 12 de Octubre, Avenida de Córdoba, Madrid, Spain

    Cristina Grávalos

  12. Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, Department of Medical Oncology, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Av. Menendez Pida, Cordoba, Spain

    Maria José Méndez-Vidal & Enrique Aranda

  13. TTD Group, Madrid, Spain

    Inmaculada Ruiz de Mena

  14. Department of Radiation Oncology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119-129, Barcelona, Spain

    Jordi Giralt

Authors
  1. Maria Alsina
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  2. Fernando Rivera
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  3. Francisco Javier Ramos
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  4. Maica Galán
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  5. Rafael López
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  6. Pilar García-Alfonso
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  7. José Enrique Alés-Martinez
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  8. Bernardo Queralt
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  9. Antonio Antón
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  10. Alfredo Carrato
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  11. Cristina Grávalos
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  12. Maria José Méndez-Vidal
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  13. Carlos López
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  14. Inmaculada Ruiz de Mena
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  15. Josep Tabernero
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  16. Jordi Giralt
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  17. Enrique Aranda
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Consortia

on behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and Grupo de Investigación Clínica en Oncología Radioterápica (GICOR)

Corresponding author

Correspondence to Maria Alsina.

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Funding

This study was supported by the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) in collaboration with the Spanish Clinical Research in Oncological Radiotherapy Group (GICOR). Support for third-party writing assistance for this manuscript, furnished by Sarah MacKenzie, was provided by Merck. Financial support for this research was provided by Merck and Sanofi Aventis. The views and opinions described in the publication do not necessarily reflect those of Merck and Sanofi Aventis.

Conflict of Interest

E. Aranda has received honoraria for an Advisory Role from Amgen, Bayer, Celgene, Merck, Roche and Sanofi.

A. Carrato has received honoraria for an Advisory Role from Merck, Bayer and Shire.

C. López has received honoraria for Consultant or Advisory Roles, Honoraria and Research Funding from Merck, Roche, Amgen, Sanofi-Aventis, Lilly, Bayer and Celgene.

F. Rivera has received honoraria for Consultant or Advisory Roles and Research Funding from Merck Serono, Roche, Amgen, Sanofi-Aventis, Lilly, Bayer and Celgene; and Honoraria from Amgen, Celgene and Lilly.

J. Tabernero has received honoraria for Consultant or Advisory Roles from Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Takeda and Taiho.

All other authors have no conflicts of interest.

Additional information

Errors were subsequently identified in the article and the following corrections should be noted:

The title of the article, which previously read “Cetuximab/TPF/radiotherapy in oesophageal cancer”

should read: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

The original article was revised.

A correction to this article is available online at https://doi.org/10.1007/s11523-017-0544-z.

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Alsina, M., Rivera, F., Ramos, F.J. et al. A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Targ Oncol 13, 69–78 (2018). https://doi.org/10.1007/s11523-017-0536-z

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