Background
Gastric cancer that has spread to the peritoneum, the thin lining of the abdominal cavity, is one of the most difficult forms of advanced cancer to treat. Once cancer cells seed the peritoneal surface, patients often develop abdominal pain, bloating, bowel obstruction, poor nutrition, and a rapid decline in health. For many years, first-line treatment has relied on systemic chemotherapy, including intravenous paclitaxel combined with S-1, an oral fluoropyrimidine widely used in East Asia. Although this approach can help control disease, survival remains limited.
A key challenge is that standard intravenous chemotherapy may not deliver high enough drug concentrations directly to the peritoneal cavity, where tumor cells are concentrated. Intraperitoneal chemotherapy was developed to address this problem by placing anticancer drugs directly into the abdominal space, potentially achieving stronger local exposure while limiting systemic toxicity. Paclitaxel is particularly attractive for this use because it has a large molecular size and remains in the peritoneal cavity longer, allowing prolonged contact with tumor implants.
However, despite promising early studies and growing clinical interest, whether adding intraperitoneal paclitaxel to standard intravenous paclitaxel plus S-1 truly improves survival had not been proven in a phase 3 randomized clinical trial. The DRAGON-01 study was designed to answer that question.
Study Objective
The purpose of this multicenter phase 3 trial was to determine whether adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 improves overall survival in patients with gastric adenocarcinoma and peritoneal metastasis.
Study Design and Participants
DRAGON-01 was an open-label, randomized, superiority trial conducted at 9 hospitals in China. Patients were enrolled from May 2017 through March 2022, and the final data cutoff was March 11, 2025.
Eligible participants were adults with gastric adenocarcinoma and peritoneal metastasis confirmed by laparoscopy. Importantly, they had no metastases outside the peritoneum and had received no prior systemic therapy. This patient population represents a common and clinically challenging subgroup in advanced gastric cancer, where treatment goals focus on prolonging survival, reducing symptoms, and preserving quality of life.
Of 246 patients assessed, 238 were randomized in a 2:1 ratio. A total of 222 patients received treatment and were included in the primary analysis.
Treatment Regimens
Patients in the intraperitoneal-plus-intravenous group, called the IP group, received paclitaxel 50 mg/m2 intravenously plus 20 mg/m2 intraperitoneally on days 1 and 8 of each 21-day cycle, together with oral S-1 at 80 mg/m2 once daily on days 1 through 14.
Patients in the comparison group, called the PS group, received paclitaxel 70 mg/m2 intravenously on days 1 and 8, together with the same oral S-1 schedule.
The treatment strategy was designed so that the total paclitaxel exposure remained similar, while the IP group received part of the drug directly into the peritoneal cavity to intensify local treatment of metastatic deposits.
Main Findings
The median follow-up time was 72.2 months, which is long enough to provide a mature survival analysis for a trial in advanced gastric cancer.
Overall survival, the primary outcome, was significantly better in the IP group. Median overall survival was 19.4 months in the IP group versus 13.9 months in the PS group. The hazard ratio for death was 0.67, meaning the risk of death was about 33% lower in the IP group during follow-up. The difference was statistically significant, with P = .01.
Progression-free survival also favored the IP group. Median progression-free survival was 11.2 months with intraperitoneal paclitaxel versus 7.2 months with intravenous paclitaxel alone in the comparison regimen. The hazard ratio for progression or death was 0.72, showing a meaningful delay in disease worsening.
In practical terms, these results suggest that directly treating the peritoneal cavity can improve disease control in a setting where systemic chemotherapy alone has often been insufficient.
Safety Results
A major concern with intraperitoneal treatment is whether adding an abdominal catheter and delivering chemotherapy locally might increase complications or severe side effects. In this trial, the safety profile was reassuring.
Grade 3 or 4 adverse events occurred in 38.5% of patients in the IP group and 41.9% in the PS group, showing no meaningful increase in severe toxicity with the intraperitoneal approach. No treatment-related deaths were reported.
This finding is important because it suggests that the potential survival benefit was not achieved at the cost of substantially greater harm. In a palliative treatment setting, maintaining tolerability is essential, since patients often need ongoing therapy over many months.
Clinical Meaning
The DRAGON-01 trial provides strong evidence that intraperitoneal paclitaxel added to intravenous paclitaxel plus S-1 can improve survival in gastric cancer with peritoneal metastasis. This is a notable development because peritoneal metastasis is one of the most treatment-resistant patterns of spread in gastric cancer.
The results support the idea that drug delivery matters as much as drug choice. By exposing peritoneal tumor deposits to higher local concentrations of paclitaxel, clinicians may be able to suppress microscopic and macroscopic disease more effectively than with intravenous therapy alone.
At the same time, these findings should be interpreted in context. The study was conducted in China, where S-1 is commonly used, and the treatment approach may not be universally available or feasible in every health system. Intraperitoneal chemotherapy also requires procedural expertise, catheter management, and careful patient selection. Therefore, implementation in routine practice will depend on local resources, training, and infrastructure.
How This Fits into Current Practice
For patients with gastric cancer that has spread only within the peritoneum, treatment decisions are complex. Options may include systemic chemotherapy, intraperitoneal therapy, clinical trials, and supportive care measures aimed at symptom control and nutrition. Some centers also consider conversion therapy strategies in selected patients who respond well to initial treatment.
This trial strengthens the evidence base for intraperitoneal therapy as a first-line option in carefully selected patients. It does not mean every patient with peritoneal metastasis should automatically receive a catheter-based regimen, but it does suggest that peritoneal-directed treatment deserves serious consideration.
The study may also encourage further research into combining intraperitoneal therapy with newer systemic agents, immunotherapy, and biomarker-driven strategies. Future studies will need to clarify which patients benefit the most, how best to deliver treatment, and whether quality-of-life outcomes improve alongside survival.
Limitations
As with any clinical trial, there are limitations. The study was open-label, meaning patients and clinicians knew which treatment was given, which can sometimes influence reporting or management decisions. The trial was also performed in a specific regional setting with established experience using S-1 and intraperitoneal chemotherapy, so results may not generalize perfectly to all countries or treatment environments.
In addition, while overall survival and progression-free survival are critical outcomes, additional details such as symptom burden, functional status, and long-term quality of life are also important for patients facing advanced disease. These endpoints help determine not only whether a treatment works, but whether it makes life better in meaningful ways.
Conclusion
In this phase 3 randomized clinical trial, adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 significantly improved overall survival and progression-free survival in patients with gastric cancer and peritoneal metastasis, without increasing severe adverse events or treatment-related deaths.
The findings provide an encouraging signal for intraperitoneal therapy as part of first-line treatment for this difficult cancer subtype. For clinicians, the study highlights the importance of targeted drug delivery to the peritoneal cavity. For patients, it offers new hope in a disease area where effective options have historically been limited.
Further studies will be valuable to confirm how best to integrate this approach into broader gastric cancer care and to identify the patients most likely to benefit.