Trevor Leong1, B Mark Smithers2, Karin Haustermans3, Michael Michael4, Val Gebski5, Danielle Miller5, John Zalcberg6, Alex Boussioutas4, Michael Findlay7, Rachel L O'Connell5, Jaclyn Verghis5, David Willis8, Tomas Kron4, Melissa Crain9, William K Murray4, Florian Lordick10, Carol Swallow11, Gail Darling12, John Simes5, Rebecca Wong13. 1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Trevor.Leong@petermac.org. 2. Upper Gastrointestinal and Soft Tissue Unit, School of Medicine, Princess Alexandra Hospital, University of Queensland, Woolloongabba, QLD, Australia. 3. Radiation Oncology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium. 4. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 5. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia. 6. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 7. Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand. 8. North West Cancer Centre, NEMSC, Tamworth, NSW, Australia. 9. TROG Cancer Research, c/o Calvary Mater Newcastle, HRMC, Waratah, NSW, Australia. 10. University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Leipzig, Germany. 11. Mount Sinai Hospital, Toronto, ON, Canada. 12. Toronto General Hospital, Toronto, ON, Canada. 13. Princess Margaret Hospital, Toronto, ON, Canada.
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.
RCT Entities:
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.
Authors: Naruhiko Ikoma; Prajnan Das; Wayne Hofstetter; Jaffer A Ajani; Jeannelyn S Estrella; Hsiang-Chun Chen; Xuemei Wang; Rashida A Callender; Cong Zhu; Christina L Roland; Keith F Fournier; Janice N Cormier; Paul Mansfield; Brian D Badgwell Journal: Gastric Cancer Date: 2018-05-05 Impact factor: 7.370
Authors: Naruhiko Ikoma; Jeannelyn S Estrella; Mariela Blum Murphy; Prajnan Das; Bruce D Minsky; Paul Mansfield; Jaffer A Ajani; Brian D Badgwell Journal: J Gastrointest Surg Date: 2020-06-15 Impact factor: 3.452