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
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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.
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.
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.
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.
KeywordsPreoperative Chemoradiation Resectable Gastric Cancer Pathological Response Rate Postoperative Chemoradiation Plan Interim Analysis
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.
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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