TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)

Abstract

BackgroundThe optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy.We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy.Methods/DesignEligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given.The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique.DiscussionTOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12609000035224. Registered 30 May 2009

Comparison of perioperative chemotherapy with adjuvant chemoradiotherapy for resectable gastric cancer: findings from a population-based study

“…More recently, CRT and PC have both been included in the US National Comprehensive Cancer Network (NCCN) treatment guidelines for resectable gastric cancer (11). However, PC and CRT have never been directly compared in a clinical trial.…”

Neoadjuvant treatment of locally advanced esophageal and junctional cancer: the evidence-base, current key questions and clinical trials

“…TOPGEAR (24). It aims to recruit 752 patients, and is powered on a projected increase in 5-year survival rate from 40% from chemotherapy alone to 50% with combination therapy.…”

“…It aims to recruit 752 patients, and is powered on a projected increase in 5-year survival rate from 40% from chemotherapy alone to 50% with combination therapy. A recent interim report from the first 120 patients randomised showed no difference in toxicity between the two arms, with grade 3 or greater toxicity observed in approximately 20% in each arm with 85-90% of patients progressing to surgery (25) Other active Phase II trials are important on this theme. In NeoSCOPE (NCT01843829), the choice of an optimal chemotherapy regimen to pair with radiation therapy (45 Gy) is examined in a phase II trial of oxaliplatin/capecitabine (OXCAP-RT) versus carboplatin/paclitaxel (CarPac-RT) (26).…”

Ocena najnowszych trendów w diagnozowaniu i leczeniu nowotworów złośliwych górnego odcinka układu pokarmowego na rok 2014 wg doniesień prezentowanych podczas konferencji ASTRO 56 w San Francisco

“…W opinii wykładowcy, czwartą, niedocenianą możliwością jest radiochemioterapia przedoperacyjna [10]. Możliwe, że wyniki toczących się badań: CRITICS, TOPGEAR oraz ARTIST II ułatwią wybór optymalnego postępowania [11,12].…”