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Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

Clinical and Translational Oncology volume 13, Article number: 179 (2011) Cite this article

Abstract

Introduction

HER2 over-expression and/or amplification are present in 9-38% of gastric or gastroesophageal junction (GEJ) cancers and are correlated to poor outcome. We conducted a multicentre phase II trial to evaluate trastuzumab in combination with cisplatin in patients with untreated HER2-positive advanced gastric or GEJ cancer.

Materials and methods

Chemo-naïve patients with measurable, non-resectable, advanced or metastatic gastric or GEJ adenocarcinoma, with HER2 over-expression and/or amplification (IHC 3+, or IHC 2+ and FISH+), age ≥18 years, ECOG ≤2, left ventricle ejection fraction ≥50% and adequate organ function were eligible. Treatment consisted of trastuzumab (8 mg/kg on cycle 1 day 1 as loading; 6 mg/kg in subsequent cycles) and cisplatin (75 mg/m2), both intravenously on day 1, every 21 days.

Results

Twenty-two out of 228 patients (10%) were HER2-positive and were included in this phase II trial. The median age was 66 years and ECOG 0/1 was 41%/59%. The median number of cycles was 4 (range 1–41). The confirmed ORR was 32% and disease control was achieved in 64% of patients. Median time to progression was 5.1 months. Grade 3 adverse events included asthenia (27%), neutropenia (18%), anorexia (14%), diarrhoea (9%) and abdominal pain (9%). There were no grade 4 toxicities or treatment-related deaths. Higher baseline HER extracellular domain (ECD) levels were associated with better outcome in terms of response and survival.

Conclusions

Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers.

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Affiliations

  1. Medical Oncology Department, University Hospital 12 de Octubre, Avda. de Andalucía, s/n, km 5.400, ES-28041, Madrid, Spain

    Cristina Grávalos, Carlos Gómez-Martín & Hernán Cortés-Funes

  2. University of Colorado Cancer Center, 12801 East 17th Avenue, Aurora, CO, 80045, USA

    Antonio Jimeno

  3. Medical Oncology Department, University Hospital Marqués de Valdecilla, Santander, Spain

    Fernando Rivera

  4. Medical Oncology Department, Hospital Carlos Haya, Málaga, Spain

    Inmaculada Alés

  5. Medical Oncology Department, Hospital Josep Trueta, Girona, Spain

    Bernardo Queralt

  6. Medical Oncology Department, Hospital Virgen de la Victoria, Málaga, Spain

    Antonia Márquez

  7. Medical Oncology Department, University Hospital La Princesa, Madrid, Spain

    Ulpiano Jiménez

  8. Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain

    Vicente Alonso

  9. Medical Oncology Unit, Hospital Severo Ochoa, Leganés, Madrid, Spain

    Rocío García-Carbonero

  10. Medical Oncology Department, University Hospital San Carlos, Madrid, Spain

    Javier Sastre

  11. MD Anderson Cancer Center España, Madrid, Spain

    Ramon Colomer

Authors
  1. Cristina Grávalos
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  2. Carlos Gómez-Martín
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  3. Fernando Rivera
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  4. Inmaculada Alés
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  5. Bernardo Queralt
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  6. Antonia Márquez
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  7. Ulpiano Jiménez
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  8. Vicente Alonso
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  9. Rocío García-Carbonero
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  10. Javier Sastre
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  11. Ramon Colomer
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  12. Hernán Cortés-Funes
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  13. Antonio Jimeno
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Corresponding authors

Correspondence to Cristina Grávalos or Antonio Jimeno.

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Grávalos, C., Gómez-Martín, C., Rivera, F. et al. Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer. Clin Transl Oncol 13, 179 (2011). https://doi.org/10.1007/s12094-011-0637-6

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  • DOI: https://doi.org/10.1007/s12094-011-0637-6

Keywords

  • Gastric cancer
  • Gastroesophageal junction adenocarcinoma
  • HER2
  • Phase II
  • Trastuzumab