Key points
- Stomach cancer is the fifth most common cancer and the fifth leading cause of cancer death worldwide [1].
- Infection with the bacterium Helicobacter pylori, a high salt intake and a diet low in fruit and vegetables are important risk factors, and treating Helicobacter infection can reduce the risk [2, 6].
- Parts of Iran, such as Golestan Province in the north of the country, are considered high-risk areas for stomach cancer [3].
- Diagnosis is made by endoscopy and biopsy; very early cancers can sometimes be removed by endoscopy alone [2].
- New treatments, including perioperative chemotherapy (FLOT), immunotherapy (nivolumab or pembrolizumab) combined with chemotherapy, and targeted drugs against HER2, have improved survival [8, 10, 13, 14]; newer drugs, such as a drug targeting claudin 18.2, have also been added to this list [15].
What is stomach cancer?
Stomach cancer develops when the cells lining the inside of the stomach grow out of control. Most stomach cancers are adenocarcinomas, which arise from the glandular cells of the stomach lining. The disease is very heterogeneous, both at the molecular level and in its appearance, and this diversity is the basis of today’s personalized treatments [2].
According to GLOBOCAN estimates for 2024, stomach cancer accounts for 4.7% of new cancer cases and 6.6% of cancer deaths worldwide, making it the fifth most common cancer and the fifth leading cause of cancer death [1].
The incidence of stomach cancer in Iran has been reported to be higher than the global average in both sexes, and it varies between the country’s provinces [4]. Golestan Province in northern Iran is one of the high-risk areas; in the province’s cancer registry study (2004 to 2016), the age-standardized incidence rate was 26.9 in men and 12.2 in women per 100,000 people [3]. About 70% of Iranian patients are men [4].
Signs and symptoms
In its early stages, stomach cancer usually has no specific symptoms, or its symptoms resemble ordinary indigestion. That is why many patients are diagnosed at an advanced stage [2]. Symptoms that should be taken seriously:
- Persistent indigestion or pain in the upper abdomen, especially if it starts for the first time after the age of 50
- Feeling full early, after eating only a small amount of food
- Unexplained weight loss and loss of appetite
- Difficulty swallowing or a feeling of food getting stuck
- Frequent nausea and vomiting, or vomiting blood
- Black, tarry stools, or iron-deficiency anemia without an obvious cause
When should I see a doctor?
Indigestion is very common and in most cases has no dangerous cause. But if it comes with weight loss, difficulty swallowing, frequent vomiting, black stools or anemia, or if it does not go away despite medication, be sure to see a doctor, who will decide whether you need an endoscopy.
Risk factors and prevention
The most important risk factors for stomach cancer are [2]:
- Chronic infection with Helicobacter pylori
- Increasing age
- High salt intake and salty or salt-preserved foods
- A diet low in fruit and vegetables
Tobacco use [2] and a family history of stomach cancer [6] are also associated with a higher risk.
The role of treating Helicobacter pylori
According to the international Maastricht VI consensus, Helicobacter pylori infection is regarded as an infectious disease, and in principle everyone who is infected should be treated; eradicating the bacterium is one of the main strategies for preventing stomach cancer [5]. In a randomized trial in South Korea in people infected with Helicobacter whose first-degree relatives had stomach cancer, eradication treatment cut the risk of stomach cancer roughly in half [6].
- If one of your first-degree relatives has had stomach cancer, talk to your doctor about testing for Helicobacter [6].
- If you have Helicobacter, complete the full course of treatment and afterwards have a test to confirm that it has been eradicated [5].
- Cut down on salt, salty pickles and salt-preserved foods, and eat more fresh fruit and vegetables [2].
- Quit smoking.
Diagnosis and staging
Diagnostic pathway for stomach cancer
- 1
Endoscopy and biopsy
Direct inspection of the esophagus and stomach and sampling of any suspicious area; the definitive diagnosis is made by histologic examination [2].
- 2
- 3
Endoscopic ultrasound and PET
Ultrasound from inside the stomach (EUS) to determine how deeply the tumor has invaded, especially in early lesions; PET-CT in selected cases [2].
- 4
- 5
- 6
Multidisciplinary team decision
The surgeon, oncologist, gastroenterologist, radiologist and pathologist decide on the treatment plan together [7].
Biomarkers and targeted therapy
| Marker | Meaning | Treatment implications |
|---|---|---|
| HER2-positive | High expression of the HER2 protein on tumor cells | Trastuzumab plus chemotherapy [10]; add pembrolizumab if CPS ≥1 [11, 21]; trastuzumab deruxtecan in the second line [12] |
| PD-L1 (CPS score) | Level of PD-L1 expression on tumor and immune cells | If CPS ≥1, immunotherapy (nivolumab or pembrolizumab) plus chemotherapy in HER2-negative disease; greater benefit at higher CPS [13, 14, 21] |
| MSI-H / dMMR | A defect in the DNA repair system | Immunotherapy alone or with chemotherapy [21] |
| Claudin 18.2 (CLDN18.2)-positive | A surface protein that is retained on stomach cancer cells | In PD-L1-negative tumors (CPS <1), add zolbetuximab to chemotherapy; in PD-L1-positive tumors, shared decision-making between this drug and immunotherapy [15, 16, 21] |
A tumor may be positive for several markers at the same time; the choice of treatment should be made by a specialist team.
Treatment by stage
Early stomach cancer
The main treatment is endoscopic removal of the tumor, without the need to remove the stomach [2].
Localized, operable disease
Surgery to remove the stomach together with D2 lymph node dissection; from stage IB onward, perioperative or adjuvant chemotherapy improves survival [2].
Perioperative chemotherapy
The FLOT regimen (every 2 weeks; 4 cycles before and 4 cycles after surgery) is the standard perioperative chemotherapy [7, 8]. In the more recent MATTERHORN trial, adding immunotherapy with durvalumab to FLOT improved event-free survival and overall survival [9, 19]; adding pembrolizumab to perioperative chemotherapy did not significantly improve survival [20].
Advanced HER2-positive disease
Advanced HER2-negative disease
In tumors with PD-L1 CPS ≥1, two-drug fluoropyrimidine- and platinum-based chemotherapy plus immunotherapy with nivolumab or pembrolizumab; the benefit grows as CPS increases [13, 14, 21]. In PD-L1-negative tumors, two-drug chemotherapy is the backbone of treatment, and if the tumor is claudin 18.2-positive, adding the newer drug zolbetuximab has improved survival [15, 16, 21].
After disease progression (second line)
Supportive care
Nutritional support, control of pain and other symptoms, and psychological support are an integral part of care at every stage of treatment.
What should I do after a diagnosis?
Frequently asked questions
Does everyone who has Helicobacter get stomach cancer?
Is stomach cancer curable?
Can antacid medicines hide the symptoms of cancer?
Antacid medicines may temporarily ease indigestion. If you have warning signs such as weight loss, difficulty swallowing or anemia, or if your symptoms do not go away with treatment, a temporary improvement should not delay an endoscopy.
Which patients is immunotherapy suitable for?
In advanced stomach cancer, immunotherapy combined with chemotherapy is more effective especially in tumors with higher PD-L1 expression [13, 14], and it is also recommended for MSI-H tumors [21]. In operable disease, adding durvalumab to FLOT chemotherapy has improved event-free survival and overall survival [9, 19].
Evidence and recent advances (for physicians)
For physicians
Perioperative therapy
In the phase 2/3 FLOT4 trial of 716 patients with locally advanced, resectable adenocarcinoma of the stomach or gastroesophageal junction, FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) increased median overall survival from 35 to 50 months compared with ECF/ECX (HR 0.77), without an increase in serious adverse events [8]. In the phase 3 MATTERHORN trial (948 patients), adding durvalumab to perioperative FLOT increased two-year event-free survival from 58.5% to 67.4% (HR 0.71) and the pathologic complete response rate from 7.2% to 19.2%, without a significant delay to surgery [9]; in the final analysis, overall survival was also significantly improved (HR 0.78; 95% CI 0.63 to 0.96) [19]. In contrast, in KEYNOTE-585, adding pembrolizumab to perioperative chemotherapy increased the pathologic complete response rate, but in the final analysis only a trend toward longer event-free survival was seen, and overall survival was not significantly improved (95% CI for the hazard ratio: 0.71 to 1.06) [20].
Immunotherapy in HER2-negative disease
In CheckMate 649 (1581 patients), nivolumab plus chemotherapy improved overall survival in patients with PD-L1 CPS ≥5, and this benefit was sustained with a minimum follow-up of 5 years (HR 0.71; 5-year overall survival 16% vs 6%); the survival benefit was also maintained in CPS ≥1 and in all randomized patients [13]. In KEYNOTE-859 (1579 patients; median follow-up 4.5 years), pembrolizumab plus chemotherapy increased median overall survival from 11.5 to 12.9 months in the overall population (HR 0.78), from 11.4 to 13.0 months in CPS ≥1 (HR 0.74) and from 11.8 to 15.8 months in CPS ≥10 (HR 0.64); in other words, the size of the benefit increases with higher PD-L1 expression [14].
Claudin 18.2: a new therapeutic target
Zolbetuximab, a monoclonal antibody against CLDN18.2, showed a survival benefit in two phase 3 trials in patients with HER2-negative, CLDN18.2-positive disease. In SPOTLIGHT (with mFOLFOX6), median PFS reached 10.61 vs 8.67 months and the risk of death was reduced (HR 0.75) [15]. In GLOW (with CAPOX), median overall survival was 14.39 vs 12.16 months (HR 0.771) [16]. Nausea and vomiting were the most common severe adverse events of zolbetuximab [15]. The ASCO guideline recommends this drug for CLDN18.2-positive tumors with PD-L1 below 1 and suggests shared decision-making for tumors positive for both PD-L1 and CLDN18.2 [21]. In the NCCN guideline, for HER2-negative, CLDN18.2-positive disease, zolbetuximab with fluoropyrimidine- and oxaliplatin-based chemotherapy is a preferred category 1 option [18].
HER2-positive disease
In the ToGA trial, adding trastuzumab to chemotherapy increased median overall survival from 11.1 to 13.8 months (HR 0.74) [10]. In KEYNOTE-811, adding pembrolizumab to trastuzumab and chemotherapy increased median progression-free survival from 8.1 to 10.0 months (HR 0.72), with the benefit seen particularly in tumors with PD-L1 CPS ≥1 [11]. In the final analysis, with a median follow-up of 50.2 months, overall survival was also significantly improved (median 20.0 vs 16.8 months; HR 0.80), and in patients with CPS ≥1 median survival was 20.1 vs 15.7 months (HR 0.79) [17]. In the NCCN guideline (version 2.2025), pembrolizumab with trastuzumab and chemotherapy is a preferred category 1 option for advanced HER2-positive disease with PD-L1 CPS ≥1 [18]. In the second line, the phase 3 DESTINY-Gastric04 trial showed that trastuzumab deruxtecan improves overall survival compared with ramucirumab + paclitaxel (median 14.7 vs 11.4 months; HR 0.70); interstitial lung disease occurred in 13.9% of patients and was mostly mild [12]. In the NCCN guideline, trastuzumab deruxtecan is a preferred option (category 2A) in the second line for HER2-positive disease that has progressed on a trastuzumab-containing regimen [18].
Second-line therapy in HER2-negative disease
In RAINBOW (665 patients), adding ramucirumab to weekly paclitaxel after progression on first-line chemotherapy increased median overall survival from 7.4 to 9.6 months (HR 0.807) [22]. In another phase 3 trial, single-agent chemotherapy with docetaxel or irinotecan increased median survival from 3.8 to 5.3 months compared with supportive care alone (HR 0.657) [23].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index11 regimens
- DPD deficiency: testing for DPYD gene variants is recommended before starting fluorouracil or capecitabine (unless treatment is urgent); avoid use in patients with variants that cause complete DPD deficiency [33, 34].
- Capecitabine and the kidneys: reduce the dose by 25% for CrCl 30 to 50 mL/min (Cockcroft-Gault); no dose has been established for CrCl below 30. Concomitant use with warfarin carries a bleeding risk, and the INR must be monitored [33].
- Oxaliplatin: acute sensory neuropathy aggravated by cold, and persistent neuropathy; for CrCl below 30, reduce the dose to 65 mg/m² [37].
- Cisplatin: dose-related, cumulative nephrotoxicity; intravenous hydration is used to reduce it, and the next dose should be given only after renal function has returned to normal; ototoxicity is cumulative, and audiometry is recommended before starting and before each dose [35].
- Docetaxel (FLOT and single-agent docetaxel): the docetaxel label recommends premedication with an oral corticosteroid (such as dexamethasone 16 mg per day, 8 mg twice daily, for 3 days starting one day before the infusion) to reduce fluid retention and hypersensitivity reactions; do not give docetaxel if neutrophils are below 1500/µL, bilirubin is above the upper limit of normal, or AST/ALT is more than 1.5 times with alkaline phosphatase more than 2.5 times the upper limit of normal [36].
- Trastuzumab: measure LVEF before starting and every 3 months during treatment; withhold trastuzumab for an absolute LVEF decrease of 16% or more, or an LVEF below normal with an absolute decrease of 10% or more [26].
- Nivolumab, pembrolizumab and durvalumab: monitor liver enzymes, creatinine and thyroid function before starting and periodically; withhold the drug for severe (grade 3) immune-related adverse events and discontinue it permanently for life-threatening (grade 4) events; dose reduction is not recommended [24, 25, 28].
For physicians
Localized resectable disease: perioperative and adjuvant therapy
Perioperative FLOT (FLOT4 trial)
Resectable adenocarcinoma of the stomach or gastroesophageal junction, clinical stage cT2 or higher and/or cN+, without distant metastasesCycle length: Every 14 days
Resectable adenocarcinoma of the stomach or gastroesophageal junction, clinical stage cT2 or higher and/or cN+, without distant metastases
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Docetaxel | 50 mg/m² | IV | Day 1 |
| Oxaliplatin | 85 mg/m² | IV | Day 1 |
| Leucovorin | 200 mg/m² | IV | Day 1 |
| Fluorouracil | 2600 mg/m² | IV, 24-h infusion | Day 1 |
Doses as in the FLOT4 trial [8].
Evidence: FLOT4 (2019)
Durvalumab + FLOT (MATTERHORN trial)
Resectable adenocarcinoma of the stomach or gastroesophageal junction, stage II to IVA (AJCC 8th edition), ECOG 0–1, no active autoimmune disease
Resectable adenocarcinoma of the stomach or gastroesophageal junction, stage II to IVA (AJCC 8th edition), ECOG 0–1, no active autoimmune disease
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Before surgery: 2 cycles | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV | Day 1 |
| FLOT | Standard FLOT doses (regimen above) | IV | Days 1 and 15 |
| After surgery: 2 cycles | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV | Day 1 |
| FLOT | Standard FLOT doses (regimen above) | IV | Days 1 and 15 |
| Maintenance: up to 10 cycles | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV | Day 1 |
Durvalumab dose and schedule from the FDA label [28]; in the MATTERHORN trial, event-free survival and overall survival were improved [9, 19]. The doses of the individual FLOT components are not stated separately in the label or the abstracts; the standard FLOT4 doses serve as the basis [8].
Evidence: MATTERHORN (2026), FLOT4 (2019), MATTERHORN (2025)
Adjuvant CAPOX (CLASSIC trial)
After curative-intent D2 gastrectomy for stage II to IIIB disease, in patients who did not receive preoperative chemotherapyCycle length: Every 21 days
After curative-intent D2 gastrectomy for stage II to IIIB disease, in patients who did not receive preoperative chemotherapy
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 130 mg/m² | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
In CLASSIC, 3-year disease-free survival was 74% vs 59% with surgery alone (HR 0.56); grade 3 or 4 adverse events occurred in 56% of patients in the chemotherapy group [32].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Advanced or metastatic disease, first-line: HER2-negative
Nivolumab + CAPOX or mFOLFOX6 (CheckMate 649 trial)
Advanced or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma, HER2-negative; FDA label: PD-L1 CPS ≥1 (greatest benefit at CPS ≥5)
Advanced or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma, HER2-negative; FDA label: PD-L1 CPS ≥1 (greatest benefit at CPS ≥5)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| 3-weekly regimen (CAPOX) | |||
| Nivolumab | 360 mg | IV (30 min) | Day 1 |
| Oxaliplatin | 130 mg/m² | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
| Or 2-weekly regimen (FOLFOX) | |||
| Nivolumab | 240 mg | IV (30 min) | Day 1 |
| Oxaliplatin | 85 mg/m² | IV | Day 1 |
| Leucovorin | 400 mg/m² | IV | Day 1 |
| Fluorouracil | 400 mg/m² | IV (bolus) | Day 1 |
| Fluorouracil | 1200 mg/m² per day (continuous infusion) | IV, continuous infusion | Days 1–2 |
Nivolumab dose from the FDA label [24] and chemotherapy doses from the original CheckMate 649 publication [31]. If chemotherapy is stopped, nivolumab monotherapy (240 mg every 2 weeks, 360 mg every 3 weeks or 480 mg every 4 weeks) continues for up to 2 years from the start of treatment [24]. The same two chemotherapy regimens without immunotherapy are the backbone treatment for tumors without a targetable marker (including PD-L1 below 1) [21].
Evidence: CheckMate 649 (2021)
Pembrolizumab + FP or CAPOX (KEYNOTE-859 trial)
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-negative; FDA label: PD-L1 CPS ≥1 (greater benefit at CPS ≥10)Cycle length: Every 21 days
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-negative; FDA label: PD-L1 CPS ≥1 (greater benefit at CPS ≥10)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg every 6 weeks) | IV (30 min), before chemotherapy | Day 1 |
| FP | |||
| Cisplatin | 80 mg/m² | IV | Day 1 |
| Fluorouracil | 800 mg/m² per day | IV, continuous infusion | Days 1–5 |
| Or CAPOX | |||
| Oxaliplatin | 130 mg/m² | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
Evidence: KEYNOTE-859 (2026)
Zolbetuximab + mFOLFOX6 or CAPOX (SPOTLIGHT and GLOW trials)
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-negative and CLDN18.2-positive (moderate to strong membranous CLDN18 staining in 75% or more of tumor cells); particularly with PD-L1 CPS below 1
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-negative and CLDN18.2-positive (moderate to strong membranous CLDN18 staining in 75% or more of tumor cells); particularly with PD-L1 CPS below 1
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Zolbetuximab | First dose 800 mg/m²; then 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks | IV, before chemotherapy (not as a bolus) | Day 1 |
| mFOLFOX6 (42-day cycle, up to 12 administrations) | |||
| Oxaliplatin | 85 mg/m² | IV | Days 1, 15 and 29 |
| Leucovorin | 400 mg/m² | IV | Days 1, 15 and 29 |
| Fluorouracil | 400 mg/m² bolus, then 2400 mg/m² continuous infusion | IV | Days 1, 15 and 29 |
| Or CAPOX (21-day cycle, up to 8 cycles) | |||
| Oxaliplatin | 130 mg/m² | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
Doses from the FDA label for zolbetuximab (description of SPOTLIGHT and GLOW) [29, 15, 16]. Before each infusion, premedication with a combination of antiemetics (such as an NK-1 and/or 5-HT3 antagonist) is required, and any existing nausea or vomiting must have improved to grade 1 or lower before the first infusion. Each infusion starts at a slow rate for the first 30 to 60 minutes (first dose 100, then 200 to 265 mg/m² per hour). Dose reduction is not recommended; adverse reactions are managed by slowing or interrupting the infusion, and the drug is permanently discontinued for a grade 4 reaction or anaphylaxis [29].
Evidence: SPOTLIGHT (2023), GLOW (2023)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Advanced or metastatic disease, first-line: HER2-positive
Trastuzumab + cisplatin + fluoropyrimidine (ToGA trial)
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive (IHC 3+ or gene amplification on FISH), with adequate cardiac function (in the trial, LVEF above 50%)Cycle length: Every 21 days
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive (IHC 3+ or gene amplification on FISH), with adequate cardiac function (in the trial, LVEF above 50%)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab | First dose 8 mg/kg (90-min infusion), then 6 mg/kg (30 to 90 min) | IV | Day 1 |
| Cisplatin | 80 mg/m² | IV (2-h infusion) | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
| Or fluorouracil (instead of capecitabine) | 800 mg/m² per day | IV, continuous infusion | Days 1–5 |
Doses from the FDA label for trastuzumab (description of the ToGA trial) [26, 10]. In tumors with PD-L1 CPS ≥1, adding pembrolizumab (next regimen) is recommended [21].
Evidence: ToGA (2010)
Pembrolizumab + trastuzumab + chemotherapy (KEYNOTE-811 trial)
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive; FDA label: PD-L1 CPS ≥1Cycle length: Every 21 days
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive; FDA label: PD-L1 CPS ≥1
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg every 6 weeks) | IV (30 min), before trastuzumab and chemotherapy | Day 1 |
| Trastuzumab | First dose 8 mg/kg, then 6 mg/kg | IV | Day 1 |
| FP | |||
| Cisplatin | 80 mg/m² (maximum 6 cycles) | IV | Day 1 |
| Fluorouracil | 800 mg/m² per day | IV, continuous infusion | Days 1–5 |
| Or CAPOX | |||
| Oxaliplatin | 130 mg/m² (maximum 6 to 8 cycles) | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
Evidence: KEYNOTE-811 (2023)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
After disease progression: second line and beyond
Ramucirumab + weekly paclitaxel (RAINBOW trial)
Advanced gastric or gastroesophageal junction adenocarcinoma progressing during or within 4 months after first-line chemotherapy (platinum + fluoropyrimidine)Cycle length: Every 28 days
Advanced gastric or gastroesophageal junction adenocarcinoma progressing during or within 4 months after first-line chemotherapy (platinum + fluoropyrimidine)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ramucirumab | 8 mg/kg | IV (60 min; if tolerated, subsequent infusions over 30 min), before paclitaxel | Days 1 and 15 |
| Paclitaxel | 80 mg/m² | IV | Days 1, 8 and 15 |
Doses from the RAINBOW trial [22] and the FDA label for ramucirumab [30]. An intravenous H1 antihistamine (e.g., diphenhydramine) is required before each ramucirumab infusion [30]; premedication for paclitaxel (corticosteroid, diphenhydramine and an H2 antagonist) as per the label [38]. Monitor blood pressure and urine protein: for urine protein of 2 g or more per 24 hours, withhold ramucirumab until it falls below 2 g, then resume at 6 mg/kg; for more than 3 g per 24 hours or nephrotic syndrome, discontinue permanently. Discontinue permanently for severe bleeding, gastrointestinal perforation or an arterial thromboembolic event; withhold 28 days before elective surgery [30]. In RAINBOW, grade ≥3 neutropenia occurred in 41% and hypertension in 14% [22].
Evidence: RAINBOW (2014)
Trastuzumab deruxtecan (DESTINY-Gastric04 trial)
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive (IHC 3+ or IHC 2+ with positive ISH), after a trastuzumab-containing regimen; in the trial, HER2 positivity was confirmed on a biopsy taken after progressionCycle length: Every 21 days
Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, HER2-positive (IHC 3+ or IHC 2+ with positive ISH), after a trastuzumab-containing regimen; in the trial, HER2 positivity was confirmed on a biopsy taken after progression
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan | 6.4 mg/kg | IV (not as a bolus; do not dilute with sodium chloride solution) | Day 1 |
Dose from the FDA label [27] and the DESTINY-Gastric04 trial [12]. Not interchangeable with trastuzumab or T-DM1. Premedication to prevent nausea and vomiting is required. The label reports interstitial lung disease (ILD) in 10% of patients with gastric cancer: for asymptomatic ILD (grade 1), withhold the drug until resolution; for symptomatic ILD (grade 2 or higher), discontinue permanently and start corticosteroids promptly. Monitor the CBC before each dose and LVEF before starting and periodically. Dose reduction: 5.4 mg/kg, then 4.4 mg/kg [27].
Evidence: DESTINY-Gastric04 (2025)
Single-agent docetaxel or irinotecan (trial by Kang et al.)
Advanced gastric cancer after one or two prior regimens containing a fluoropyrimidine and platinum, ECOG 0–1Each drug’s schedule in the table
Advanced gastric cancer after one or two prior regimens containing a fluoropyrimidine and platinum, ECOG 0–1
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Docetaxel | 60 mg/m² | IV | Day 1 (every 3 weeks) |
| Or irinotecan | 150 mg/m² | IV | Day 1 (every 2 weeks) |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
12 itemsPerioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial
Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer
Pembrolizumab plus chemotherapy as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma: 4.5-year follow-up from the randomized phase III KEYNOTE-859 study
Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649
Family History of Gastric Cancer and Helicobacter pylori Treatment
Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial
Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial
Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial
Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer
Clinical guidelines
2 itemsReferences
39 referencesShow all references, 20 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3Trends in the Incidence of Stomach Cancer in Golestan Province, a High-risk Area in Northern Iran, 2004-2016
- 4Trend of geographical distribution of stomach cancer in Iran from 2004 to 2014
- 5
- 6
- 7
- 8Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 16
- 17Pembrolizumab in HER2-Positive Gastric Cancer
- 18
- 19Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 20
- 21
- 22
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial
- 32Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial
- 33
- 34Fluorouracil injection, for intravenous use: Prescribing Information
- 35Cisplatin injection: Prescribing Information
- 36Docetaxel injection, for intravenous use: Prescribing Information
- 37Oxaliplatin injection, for intravenous use: Prescribing Information
- 38Paclitaxel injection: Prescribing Information
- 39CAMPTOSAR (irinotecan hydrochloride) injection, for intravenous use: Prescribing Information
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.