Chemo into the abdomen lengthens survival in gastric cancer with spread

Delivering the chemotherapy drug paclitaxel directly into the abdominal cavity, on top of standard intravenous treatment, extended survival in gastric cancer that had spread to the lining of the abdomen: in the phase 3 DRAGON-01 trial, median overall survival was 19.4 months with the added intraperitoneal drug against 13.9 months without [s1]. The hazard ratio for death was 0.67 (95% confidence interval, 0.50 to 0.90; p=0.01), and severe side-effects were no more common in the intensively treated group [s1].

Gastric cancer that reaches the peritoneum — the membrane lining the abdominal cavity — is among the hardest forms to treat. The disease is no longer confined to the stomach but has not necessarily spread to distant organs either, and intravenous drugs reach the thin sheets of tumour studding the peritoneum poorly. That is the rationale for intraperitoneal chemotherapy: infusing the drug into the cavity itself achieves far higher local concentrations than the bloodstream delivers [s1]. The approach has been used for years, but whether it actually prolongs life had not been settled in a phase 3 randomised trial [s1].

What they did

DRAGON-01 was an open-label superiority trial run at nine hospitals in China, enrolling patients from May 2017 to March 2022 with a data cutoff of 11 March 2025 [s1]. It recruited adults with gastric adenocarcinoma and laparoscopically confirmed peritoneal metastasis, no spread beyond the peritoneum, and no prior systemic therapy — a defined, biopsy-confirmed population rather than a mixed one [s1]. Of 246 patients assessed, 238 were randomly assigned 2:1, and 222 received treatment and formed the primary analysis [s1]. The trial was registered as ChiCTR-IIR-16009802 [s2].

The intraperitoneal group received paclitaxel both intravenously (50 mg/m²) and into the abdominal cavity (20 mg/m²) on days 1 and 8 of each 21-day cycle, plus the oral fluoropyrimidine S-1 at 80 mg/m² on days 1 to 14 [s1]. The comparison group received a higher intravenous paclitaxel dose (70 mg/m²) on the same schedule with the same S-1 backbone [s1]. The primary endpoint was overall survival; progression-free survival and safety were secondary [s1]. Median follow-up was long, at 72.2 months [s1].

What it showed

Median overall survival was 19.4 months (95% confidence interval, 17.1 to 22.9) in the intraperitoneal group and 13.9 months (10.3 to 16.1) in the intravenous-only group, a hazard ratio for death of 0.67 (95% confidence interval, 0.50 to 0.90; p=0.01) [s1]. Median progression-free survival followed the same direction: 11.2 months (9.3 to 14.0) against 7.2 months (5.7 to 11.6), hazard ratio 0.72 (0.54 to 0.96) [s1]. A 5.5-month gain in median survival is substantial in a setting where treatment is generally regarded as controlling rather than curing the disease [s1].

Two caveats sit alongside the result. The trial was open-label — patients and doctors knew which treatment was given — which can influence subjective decisions, though overall survival is among the least biasable endpoints. And it was conducted entirely in China, where gastric cancer is common and surgical and interventional expertise in it is concentrated; whether the same procedure delivers the same margin elsewhere is untested here [s1].

The cost side

The more intensive regimen did not cost more in serious toxicity. Grade 3 or 4 adverse events occurred in 38.5% of the intraperitoneal group and 41.9% of the intravenous-only group, and no treatment-related deaths occurred in either arm [s1]. That the added intra-abdominal drug did not raise severe side-effects is part of why the authors frame it as an encouraging signal for first-line use — the survival gain came without a matching penalty in harm [s1]. Intraperitoneal delivery does require repeated access to the abdominal cavity, a practical burden the survival numbers alone do not capture.

What to watch

DRAGON-01 provides the first phase 3 randomised evidence that adding intraperitoneal paclitaxel to standard chemotherapy prolongs survival in this specific, biopsy-confirmed setting [s1]. It does not speak to gastric cancer that has spread beyond the peritoneum, nor does it settle how the approach compares with the newer antibody-based regimens now entering first-line care, such as the HER2-targeted treatments approved for gastro-oesophageal disease. And as with most gastric cancer, the largest survival gains are won earlier: in countries with organised endoscopic screening programmes, far more disease is caught before it ever reaches the peritoneum.

Sources

• [s1] Intraperitoneal and Intravenous Paclitaxel Plus S-1 for Gastric Cancer With Peritoneal Metastasis: A Phase 3 Randomized Clinical Trial (DRAGON-01). JAMA Oncology. 2026;12(7):732-740. doi:10.1001/jamaoncol.2026.1347.
• [s2] Chinese Clinical Trial Registry. Intraperitoneal Paclitaxel Plus Systemic Chemotherapy for Gastric Cancer With Peritoneal Metastasis (DRAGON-01, ChiCTR-IIR-16009802).