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Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by gemcitabine–erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD 10-03 trial)

  • Joan Maurel
  • Santiago Sánchez-Cabús
  • Berta Laquente
  • Lydia Gaba
  • Laura Visa
  • Joan Fabregat
  • Ignacio Povés
  • Susana Roselló
  • Roberto Díaz-Beveridge
  • Marta Martín-Richard
  • Javier Rodriguez
  • Luis Sabater
  • Carles Conill
  • María Cambray
  • Ana Reig
  • Juan Ramón Ayuso
  • Carlos Valls
  • Antonio Ferrández
  • Josep Antoni Bombí
  • Angels Ginés
  • Xabier García-Albéniz
  • Laureano Fernández-Cruz
Original Article

Abstract

Background

Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.

Methods

Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon’s design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.

Results

Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4–36.2) and 12.8 months (95% CI 8.6–17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009).

Conclusion

The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

Keywords

Neoadjuant Pancreatic Adenocarcinoma 

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study are in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Joan Maurel
    • 3
  • Santiago Sánchez-Cabús
    • 1
  • Berta Laquente
    • 2
  • Lydia Gaba
    • 3
  • Laura Visa
    • 4
  • Joan Fabregat
    • 5
  • Ignacio Povés
    • 6
  • Susana Roselló
    • 7
  • Roberto Díaz-Beveridge
    • 8
  • Marta Martín-Richard
    • 9
  • Javier Rodriguez
    • 10
  • Luis Sabater
    • 11
  • Carles Conill
    • 12
  • María Cambray
    • 13
  • Ana Reig
    • 14
  • Juan Ramón Ayuso
    • 15
  • Carlos Valls
    • 16
  • Antonio Ferrández
    • 17
  • Josep Antoni Bombí
    • 18
  • Angels Ginés
    • 19
  • Xabier García-Albéniz
    • 20
  • Laureano Fernández-Cruz
    • 1
  1. 1.Surgical Department, Hospital Clínic BarcelonaIDIBAPS, University of BarcelonaBarcelonaSpain
  2. 2.Medical Oncology DepartmentInstitut Català d’OncologiaHospitaletSpain
  3. 3.Medical Oncology Department, Hospital Clínic, Translational Genomics and Targeted Therapeutics in Solid Tumors GroupIDIBAPS, University of BarcelonaBarcelonaSpain
  4. 4.Department of OncologyHospital MarBarcelonaSpain
  5. 5.Surgical DepartmentHospital BellvitgeHospitaletSpain
  6. 6.Surgical DepartmentHospital del MarBarcelonaSpain
  7. 7.Medical Oncology DepartmentHospital Clínico ValenciaValenciaSpain
  8. 8.Medical Oncology DepartmentHospital La FeValenciaSpain
  9. 9.Medical Oncology DepartmentHospital Sant PauBarcelonaSpain
  10. 10.Medical Oncology DepartmentHospital Clínico Universitario NavarraPamplonaSpain
  11. 11.Surgical DepartmentHospital Clínico ValenciaValenciaSpain
  12. 12.Radiotherapy Oncology Department, Hospital Clínic BarcelonaIDIBAPS, University of BarcelonaBarcelonaSpain
  13. 13.Radiotherapy Oncology DepartmentInstitut Català d’OncologiaHospitaletSpain
  14. 14.Radiotherapy Oncology DepartmentHospital MarBarcelonaSpain
  15. 15.Radiology Department, Hospital Clínic BarcelonaIDIBAPS, University of BarcelonaBarcelonaSpain
  16. 16.Radiology DepartmentHospital BellvitgeHospitaletSpain
  17. 17.Pathology DepartmentHospital Clínico ValenciaValenciaSpain
  18. 18.Pathology Department, Hospital Clínic BarcelonaIDIBAPS, University of BarcelonaBarcelonaSpain
  19. 19.Gastrointestinal Department, Hospital Clínic BarcelonaIDIBAPS, University of BarcelonaBarcelonaSpain
  20. 20.Harvard T.H. Chan School of Public HealthBostonUSA

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