Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)

Abstract

BackgroundRadical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively.Methods/designIn this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate.ConclusionResults of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer.Trial registrationclinicaltrials.gov NCT00407186

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus

“…Currently, both strategies are also being investigated prospectively in the CRITICS trial [59]. Additionally, a comparative French multicenter study suggested a worse outcome for patients with a signet ring cell type of gastric carcinoma after perioperative chemotherapy versus surgery [60].…”

Adjuvant Treatment for Gastric Cancer: Chemotherapy Versus Radiation

“…These factors limit the generalizability of studies conducted in one part of the world, and the question remains: Can we replicate outcomes from CLASSIC and ARTIST trials in the Western population? The ChemoRadiotherapy after Induction chemoTherapy In Cancer of the Stomach (CRITICS) trial is currently accruing participants and will likely be helpful in this regard [55]. In this Dutch trial, all patients will receive three cycles of preoperative chemotherapy with epirubicin, capecitabine, and cisplatin, followed by adequate resection.…”

A Review of Capecitabine-Based Adjuvant Therapy for Gastric Cancer in the Chinese Population

“…Compared with FOLFOX [14][15][16][17][18][19], XELOX has shown better or similar efficacy and a lower incidence of toxicity, and compared with the XELLOBA and SOX regimens [20,21] it has shown equivalent efficacy and a similar safety profile. It is notable that while no survival benefit from S-1 was observed in elderly AGC patients ≥70 years of age [53], capecitabine had promising survival benefits (2-year OS: 77-80%) and favorable tolerance [41][42][43][44] and may be a good choice for this subgroup of patients.…”

“…Another Phase III multicenter study (CRITICS) aimed to assess whether the combination of preoperative chemotherapy and postoperative CRT can improve the clinical outcome compared with the current European standard of perioperative chemotherapy [21]. It is well accepted that postoperative regional radiation plus chemotherapy reduces the risk of relapse and prolongs survival in high-risk AGC patients following D0 or D1 dissection.…”

“…Although postoperative CRT after D0 or D1 dissection (a standard option in Europe and the USA) showed significant survival benefit [20,21], postoperative CRT after D2 dissection (a standard option in east Asia) did not contribute to any significant reduction in the risk of recurrence in the ARTIST trial in South-Korean patients [35]. While most patients in the INT0116 study [20] had T3/T4 disease and 85% had nodal metastases, almost 60% of patients had early stage disease (IB/IIA) in the ARTIST trial [35].…”