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.
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.
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Trevor.Leong@petermac.org.
Trevor
T
Leong
Upper Gastrointestinal and Soft Tissue Unit, School of Medicine, Princess Alexandra Hospital, University of Queensland, Woolloongabba, QLD, Australia.
B Mark
BM
Smithers
Radiation Oncology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium.
Karin
K
Haustermans
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Michael
M
Michael
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Val
V
Gebski
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Danielle
D
Miller
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
John
J
Zalcberg
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Alex
A
Boussioutas
Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand.
Michael
M
Findlay
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Rachel L
RL
O'Connell
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Jaclyn
J
Verghis
North West Cancer Centre, NEMSC, Tamworth, NSW, Australia.
David
D
Willis
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Tomas
T
Kron
TROG Cancer Research, c/o Calvary Mater Newcastle, HRMC, Waratah, NSW, Australia.
Melissa
M
Crain
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
William K
WK
Murray
University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Leipzig, Germany.
Florian
F
Lordick
Mount Sinai Hospital, Toronto, ON, Canada.
Carol
C
Swallow
Toronto General Hospital, Toronto, ON, Canada.
Gail
G
Darling
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
John
J
Simes
Princess Margaret Hospital, Toronto, ON, Canada.
Rebecca
R
Wong
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019990:Perioperative Care; D011300:Preoperative Care; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate
D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil