From the Guidelines

Chemotherapy for gastric cancer typically involves a combination of platinum-based and fluoropyrimidine-based regimens.

ECF (epirubicin, cisplatin, and 5-FU), which has been shown to be effective in improving survival and quality of life compared to best supportive care 1
DCF (docetaxel, cisplatin, and 5-FU), although it is associated with increased myelosuppression and infectious complications 1
Capecitabine and oxaliplatin, which have been shown to be as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer 1
Trastuzumab plus chemotherapy, which is recommended as first-line therapy for patients with HER2 overexpression–positive tumors 1
Nivolumab combined with chemotherapy, which is recommended as first-line therapy for tumors with PD-L1 expression levels by CPS of $5 (category 1) or CPS of ,5 (category 2B) 1

Ramucirumab, as a single agent or in combination with paclitaxel, which has been shown to have a survival benefit for patients with advanced gastric adenocarcinoma progressing after first-line chemotherapy 1
Pembrolizumab, which is recommended for patients with MSI-H/dMMR or TMB-H tumors 1
Dostarlimab-gxly, which is an alternative option to pembrolizumab for MSI-H/dMMR tumors 1
Entrectinib and larotrectinib, which are recommended for second-line or subsequent therapy for NTRK gene fusion-positive tumors 1

From the Research

The chemotherapy regimen for gastric cancer varies depending on the stage and patient's condition.

For unresectable and/or recurrent gastric cancer, first-line chemotherapy consists of multidrug regimens including oral 5-FU agents such as S1/Xeloda and platinum preparations, as well as Trastuzumab, which is effective in HER2-positive cases 2.
Second- and third-line chemotherapy regimens include taxanes, Ramucirumab (R-mab), and Nivolumab (N-mab), which have different mechanisms of action from first-line chemotherapy 2.
In Eastern countries, postoperative adjuvant chemotherapy has been successful, including S1, Docetaxel/S1 (DS), and Xeloda/Oxaliplatin (Xelox) regimens, whereas, in Western countries, the 5-FU/Leucovorin/Oxaliplatin/Docetaxel (FLOT) regimen was recently shown to be effective in the perioperative chemotherapy setting 2.
For stage IV gastric cancer, new therapeutic strategies have been proposed such as neoadjuvant chemotherapy and conversion surgery, and cures can be conditionally obtained 2.

Combination chemotherapy has been shown to improve survival in patients with advanced gastric cancer.

The comparison of combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (hazard ratio 0.82; 95% confidence interval 0.74 to 0.90,1914 participants) 3.
Two- and three-drug regimens including 5-FU, cisplatin, with or without an anthracycline, as well as irinotecan or docetaxel-containing regimens are reasonable treatment options for HER-2 negative patients 3.
The price of this benefit is increased toxicity as a result of combination chemotherapy 3.

Targeted therapies have also been investigated in the treatment of gastric cancer.

Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer 4.
Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients 4.

Chemotherapy regimens have also been studied in elderly patients with advanced gastric cancer.

Combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment has been shown to be effective and well-tolerated in elderly patients with advanced gastric cancer 5.
The overall objective response rate was 54.2% (95% CI, 45.3-63.1%), with a median time to progression of 6.9 months (95% CI, 5.5-8.3 months) and a median overall survival of 12.8 months (95% CI, 11.4-14.2 months) 5.