FLOT4: What the Stomach Cancer Trial Found

Chemotherapy on both sides of the operation

Stomach cancer that has not spread is treated with surgery. A surgeon removes part or all of the stomach, plus nearby lymph nodes. Surgery alone is often not enough. Cancer cells can slip away from the tumor before the operation and settle where no scan can see them.

European practice answered that with perioperative chemotherapy. Perioperative means around the operation: drugs before surgery, then more drugs after it. The first half shrinks the tumor and makes a clean removal more likely. The second half goes after cells left behind.

FLOT4 did not test that idea. It took the idea as settled and asked a narrower question. Which drugs?

Two regimens, 716 patients, 38 German centers

Between August 2010 and February 2015, FLOT4 enrolled 716 people at 38 German hospitals and oncology practices. All had gastric or gastro-esophageal junction adenocarcinoma. Adenocarcinoma is cancer that starts in gland cells, and nearly all stomach cancers are this type. The gastro-esophageal junction is where the food pipe meets the stomach.

Everyone had disease that a surgeon could remove. Tumors were clinical stage cT2 or higher, or had spread to lymph nodes, or both. Nobody had spread to distant organs.

Half were assigned the older regimen, called ECF or ECX. That is epirubicin, cisplatin, and either fluorouracil or capecitabine, given in three cycles before surgery and three after.

The other half got FLOT. That is fluorouracil, leucovorin, oxaliplatin and docetaxel, given in four shorter cycles before surgery and four after. Leucovorin is not a chemotherapy drug; it makes fluorouracil work better.

The main measure was overall survival. That means how long people lived, counted from the day they entered the trial, whatever the cause of death.

A 15-month difference in the middle of the curve

People given FLOT lived a median of 50 months. People given ECF or ECX lived a median of 35 months. Median means the halfway point: half the group lived longer, half less.

The hazard ratio was 0.77, with a 95 percent confidence interval of 0.63 to 0.94. A hazard ratio compares the rate of death between two groups. A value of 0.77 means the rate was about 23 percent lower with FLOT. The confidence interval is the range the true value most likely sits in. It stayed below 1.0, so the result was unlikely to be chance.

The side effects did not get worse

Trials that add drugs usually cost the patient something. This one did not.

Serious treatment-related side effects hit 97 of 356 people on FLOT, or 27 percent. On ECF or ECX the figure was 96 of 360, also 27 percent. Two people in each group died of treatment toxicity, under 1 percent on both sides. Hospital stays for toxicity ran at 25 percent with FLOT and 26 percent with the older regimen.

That balance is why FLOT4 changed practice. A gain this size normally comes with a price tag, and here the price tag was flat.

When to get checked

Early stomach cancer usually causes nothing at all. NCI notes that symptoms tend to start only after the cancer has spread. That is the hard part of this disease.

NCI lists these as possible early signs:

• Indigestion and stomach discomfort
• Feeling bloated after eating
• Mild nausea
• Loss of appetite
• Heartburn

And these as signs of more advanced disease:

• Blood in the stool
• Vomiting
• Weight loss with no known cause
• Stomach pain
• Yellowing of the eyes or skin, called jaundice
• Trouble swallowing

Almost every one of these has a common, harmless cause. That is exactly why they get ignored. Worth a doctor's visit is the pattern that does not settle: weeks of it, not days, or any blood at all.

How the diagnosis gets made

The main test is upper endoscopy. A thin lighted tube goes down the throat, and the doctor takes a tissue sample. That sample is checked for cancer, for Helicobacter pylori infection, and for biomarkers.

Biomarker testing matters for treatment choice. NCI lists HER2, PD-L1, microsatellite instability, mismatch repair deficiency, tumor mutational burden and NTRK gene changes among the things labs look for in stomach cancer. Our page on biomarker testing walks through what each one changes.

Staging then uses CT scans, endoscopic ultrasound and sometimes PET-CT. Endoscopic ultrasound sends sound waves from the tip of the scope to show how deep the tumor has grown into the stomach wall. Depth is what the T in TNM staging measures.

The wider picture from SEER

The American Cancer Society projects 31,510 new US stomach cancer cases and 10,740 deaths for 2026, and SEER, NCI's cancer surveillance program, republishes them. SEER's own count puts the median age at diagnosis at 68.

Five-year relative survival is 39.8 percent across all cases from 2016 to 2022. By stage it splits sharply: 78.1 percent while the cancer is confined to the stomach, 39.0 percent once it reaches nearby lymph nodes, and 8.1 percent when it has spread to distant organs. Only 32 percent are caught while still confined. Thirty-five percent are already distant.

These are group averages from thousands of records. They describe a population, not any one person, and they include people treated long before FLOT existed. Our page on stomach cancer treatment by stage covers what each of those stages usually involves.

What this trial cannot tell you

Every patient was treated in Germany. Surgical practice, and how many lymph nodes get removed, differs between countries. The trial cannot say whether the same gap would appear elsewhere.

It was open-label. Patients and doctors knew which regimen they were on.

The comparison arm is now dated. ECF and ECX are no longer the alternative anyone is choosing. FLOT4 says nothing about how FLOT compares with today's rivals, such as chemotherapy combined with immunotherapy.

And FLOT is demanding. It runs on a two-week cycle rather than three, and it requires a person fit enough to take four cycles, then major surgery, then four more. Fitness for the regimen is a real gate. Our page on chemotherapy explains what a cycle involves.

Sources

• Al-Batran SE and others, FLOT4, The Lancet 2019 (record and abstract via NCBI) — https://pubmed.ncbi.nlm.nih.gov/30982686/
• NCI, Symptoms of Stomach Cancer — https://www.cancer.gov/types/stomach/symptoms
• NCI, Stomach Cancer Diagnosis — https://www.cancer.gov/types/stomach/diagnosis
• NCI PDQ, Gastric Cancer Treatment (Health Professional Version) — https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq
• SEER Cancer Stat Facts, Stomach Cancer — https://seer.cancer.gov/statfacts/html/stomach.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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