Neoadjuvant Chemoradiotherapy vs. Chemotherapy Followed by Radical Gastrectomy and Adjuvant Chemotherapy for Advanced Gastric Cancer

Conditions

Gastric Cancer

Keywords

Neoadjuvant, Chemoradiotherapy, Chemotherapy, Locally advanced gastric cancer, Pathological complete response, D2 gastrectomy

Brief summary

Patients with histologically confirmed gastric adenocarcinoma with locally advanced gastric cancer are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy or neoadjuvant chemotherapy alone using XELOX regimen following D2 gastrectomy and adjuvant chemotherapy for 3 cycles. The primary end point is 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, pathological complete remission (pCR) and treatment safety.

Detailed description

Background: Literatures have shown that patients with locally advanced gastric cancer could potentially benefit from neoadjuvant chemoradiotherapy, but whether this can improve patients' outcome is still unclear. Patients and methods: In this study , patients with histologically confirmed gastric adenocarcinoma with pre-operative staging are cT3N2/N3M0, cT4aN+M0 and cT4bNanyM0, aged between 18-75 years old, with adequate organ function and having an Eastern Cooperative Oncology Group performance status score ≤2, are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy \[Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy)\] or neoadjuvant chemotherapy alone using XELOX regimen (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following by D2 gastrectomy and adjuvant chemotherapy with same dosage of XELOX therapy for up to 3 cycles. The primary end point is 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, pathological complete remission (pCR) and treatment safety. The final study analytics are to be conducted at the end of the 5th year after the last patient's enrollment.

Rui-Hua Xu, W Wang, Y M Zhang, Yong Li, Yongxiang Li et al. (17 authors)

Journal of Clinical Oncology2026-06-03

10.1200/jco.2026.44.17_suppl.lba4075

Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial.

Wang JJ, Shao H, Zhang L, Jing M, Xu WJ, Sun HW, Zhou ZW, Zhang YJ.

2023-06-092 citations

10.1186/s13014-023-02269-6

Total neoadjuvant therapy for locally advanced gastric cancer and esophagogastric junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase II clinical trial.

Shi J, Li N, Tang Y, Jiang L, Yang L, Wang S, Song Y, Liu Y, Fang H, Lu N, Qi S, Chen B, Li Z, Liu S, Wang J, Wang W, Zhu S, Yang J, Li Y, Zhao D, Jin J.

2022-07-288 citations

10.1186/s12876-022-02440-5

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

Zhou M, Yang W, Xuan Y, Zou W, Wang Y, Zhang Z, Zhang J, Mo M, Zhou C, Liu Y, Zhang W, Zhang Z, He Y, Weng W, Tan C, Wang L, Huang D, Sheng W, Li H, Zhu H, Wang Y, Shen L, Zhang H, Wan J, Li G, Huang H, Wang Y, Zhang Z, Liu X, Xia F.

2022-06-281 citations

10.1186/s12885-022-09786-9

Dose-Effect Analysis of Radiation-Induced Liver Disease During Preoperative Chemoradiotherapy for Locally Advanced Gastric Cancer.

Li N, Feng LL, Zhang YJ, Wang JJ, Zhang YT, Zhang L, Huang SM, Zhou ZW.

2021-11-01

10.1016/j.ijrobp.2021.07.461

Abstract 6498: Preoperative treatment remodels immune microenvironment via decreasing pro-tumorigenic and increasing anti-tumorigenic immune cells in the locally advanced gastric cancer

Yi Fang, Yujing Zhang, Nai Li, Yihong Ling, Zhiwei Zhou

Cancer Research2020-08-15

10.1158/1538-7445.am2020-6498

Interventions

RADIATIONNeoadjuvant Chemoradiotherapy

Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy \[Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy)\]

DRUGNeoadjuvant Chemotherapy

3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle)

PROCEDURER0 D2 Gastrectomy

DRUGAdjuvant Chemotherapy

3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Neoadjuvant Chemoradiotherapy versus Neoadjuvant Chemotherapy

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

Inclusion criteria

1. Histologically confirmed gastric cancer with clinical staging determined by endoscopic ultrasound and contrast-enhanced CT or MRI as cT3N2/N3M0, cT4aN+M0, or cT4bNanyM0. 2. Good general condition, with Eastern Cooperative Oncology Group (ECOG) performance status \<2 and no contraindications to surgery. 3. Ambulatory male or female patients aged 18 to 75 years. 4. Sufficient physical fitness and organ function to tolerate major abdominal surgery. 5. Baseline laboratory parameters meeting the following criteria: WBC \> 4.0 × 10⁹/L, ANC \> 1.5 × 10⁹/L, Hb ≥ 100 g/L, PLT ≥ 100 × 10⁹/L, total bilirubin ≤ 1.5 × upper limit of normal (ULN), AST and ALT ≤ 2.5 × ULN, and serum creatinine ≤ 1.0 × ULN. 6. No prior or concurrent diagnosis of other malignancies. 7. Willing and able to comply with study protocol requirements during the trial period. 8. Provided written informed consent prior to screening, with full awareness of the right to withdraw from the study at any time without consequence. 9. Estimated life expectancy of at least 3 months.

Exclusion criteria

1. Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception. 2. Receipt of any antitumor therapy prior to surgery. 3. History of or concurrent malignancies other than gastric cancer. 4. Presence of psychiatric disorders, brain metastases, or leptomeningeal metastases. 5. Uncontrolled or severe comorbid conditions or active infections. 6. Decompensated dysfunction of major organs (e.g., cardiac, pulmonary, hepatic, or renal failure). 7. Concurrent participation in another clinical trial. 8. Contraindications to chemotherapy, radiotherapy, or surgery. 9. Active hepatitis B or hepatitis C virus infection. 10. Grade ≥2 peripheral neuropathy (per NCI-CTCAE). 11. Chronic intestinal diseases or short bowel syndrome. 12. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 13. Known hypersensitivity to capecitabine or any of its excipients. 14. Ongoing treatment with sorivudine or related analogs. 15. Deemed unsuitable for participation in this clinical trial by the investigator.

Design outcomes

Primary

Measure	Time frame	Description
Disease-free Survival	3 years	3-year DFS

Secondary

Measure	Time frame	Description
Overall Survival	5 years	5-year Overall Survival
Pathological Complete Remission	Peri-operative period	pCR
Radical Resection Rate	Peri-operative period	R0 Resection Rate
Adverse effects	Peri-operative period	Treatment safety

Countries

China

Outcome results

None listed