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TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Postoperative chemoradiation and perioperative chemotherapy using epirubicin/cisplatin/5-fluorouracil (ECF) represent two standards of care for resectable gastric cancer. In the TOPGEAR (Trial Of Preoperative therapy for Gastric and Esophagogastric junction AdenocaRcinoma) trial, we hypothesized that adding preoperative chemoradiation to perioperative ECF will improve survival; however, the safety and feasibility of preoperative chemoradiation have yet to be determined.

Methods

TOPGEAR is an international phase III trial in which patients with adenocarcinoma of the stomach were randomized to perioperative ECF alone or with preoperative chemoradiation. The ECF-alone group received three preoperative cycles of ECF, while the chemoradiation group received two cycles of preoperative ECF followed by chemoradiation. Both groups received three postoperative cycles of ECF. A planned interim analysis of the first 120 patients was conducted, and was reviewed by the Independent Data Safety Monitoring Committee to assess treatment compliance, toxicity/safety, and response rates.

Results

The proportion of patients who received all cycles of preoperative chemotherapy was 93% (ECF group) and 98% (chemoradiation group), while 65 and 53%, respectively, received all cycles of postoperative chemotherapy. Overall, 92% of patients allocated to preoperative chemoradiation received this treatment. The proportion of patients proceeding to surgery was 90% (ECF group) and 85% (chemoradiation group). Grade 3 or higher surgical complications occurred in 22% of patients in both groups. Furthermore, grade 3 or higher gastrointestinal toxicity occurred in 32% (ECF group) and 30% (chemoradiation group) of patients, while hematologic toxicity occurred in 50 and 52% of patients.

Conclusions

These results demonstrate that preoperative chemoradiation can be safely delivered to the vast majority of patients without a significant increase in treatment toxicity or surgical morbidity.

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Acknowledgement

This work was supported by grants from the National Health and Medical Research Council (1046425), Canadian Institutes of Health Research (CIHR) Grant No. 119445, the Canadian Cancer Society Research Institute (CCSRI) Grant No. 021039, the Health Research Council of New Zealand (HRC) International Investment Opportunities Fund (contract number 09/624), the EORTC Cancer Research Fund, and the Cancer Australia Priority-Driven Collaborative Research Scheme (Project ID 570996). Rhana Pike, from the National Health and Medical Research Council (NHMRC) Clinical Trials Centre, assisted with the manuscript.

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Authors and Affiliations

  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Trevor Leong MD, Michael Michael MD, Alex Boussioutas MD, Tomas Kron PhD & William K. Murray MD

  2. Upper Gastrointestinal and Soft Tissue Unit, School of Medicine, Princess Alexandra Hospital, University of Queensland, Woolloongabba, QLD, Australia

    B. Mark Smithers MD

  3. Radiation Oncology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium

    Karin Haustermans MD

  4. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia

    Val Gebski MSat, Danielle Miller MPH, Rachel L. O’Connell PhD, Jaclyn Verghis MIntS & John Simes MD

  5. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    John Zalcberg MD

  6. Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand

    Michael Findlay MD

  7. North West Cancer Centre, NEMSC, Tamworth, NSW, Australia

    David Willis MTech (IT)

  8. TROG Cancer Research, c/o Calvary Mater Newcastle, HRMC, Waratah, NSW, Australia

    Melissa Crain BBus

  9. University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Leipzig, Germany

    Florian Lordick MD

  10. Mount Sinai Hospital, Toronto, ON, Canada

    Carol Swallow MD

  11. Toronto General Hospital, Toronto, ON, Canada

    Gail Darling MD

  12. Princess Margaret Hospital, Toronto, ON, Canada

    Rebecca Wong MD

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  1. Trevor Leong MD
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  2. B. Mark Smithers MD
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  4. Michael Michael MD
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  15. William K. Murray MD
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  16. Florian Lordick MD
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  17. Carol Swallow MD
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  18. Gail Darling MD
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  19. John Simes MD
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Corresponding author

Correspondence to Trevor Leong MD.

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Disclosures

Florian Lordick has financial activities with the following companies, outside the submitted work: Amgen, Bionten, Boston Biomedical, Boehringer Ingelheim, Ganymed, GSK, Fresenius Biotech, Lilly, MSD, Nordic, Roche, and Taiho.

Trevor Leong, B. Mark Smithers, Karin Haustermans, Michael Michael, Val Gebski, Danielle Miller, John Zalcberg, Alex Boussioutas, Michael Findlay, Rachel L. O’Connell, Jaclyn Verghis, David Willis, Tomas Kron, Melissa Crain, William K. Murray, Carol Swallow, Gail Darling, John Simes, Rebecca Wong have declared no conflicts of interest.

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Leong, T., Smithers, B.M., Haustermans, K. et al. TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol 24, 2252–2258 (2017). https://doi.org/10.1245/s10434-017-5830-6

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  • DOI: https://doi.org/10.1245/s10434-017-5830-6

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