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 stomach cancer to treat. Once cancer cells seed the peritoneal surface, patients often develop abdominal fluid buildup, bowel symptoms, poor nutritional status, and a limited response to standard systemic chemotherapy. Survival has historically been short, even with widely used first-line regimens such as intravenous paclitaxel combined with S-1, an oral fluoropyrimidine commonly used in East Asia.
One treatment strategy that has attracted growing interest is intraperitoneal chemotherapy. By delivering anticancer drugs directly into the abdominal cavity, physicians can expose peritoneal tumor deposits to higher local drug concentrations while potentially reducing whole-body toxicity. Paclitaxel is especially suitable for this approach because it remains in the peritoneal cavity longer than many other drugs. The DRAGON-01 trial was designed to answer a key question: can adding intraperitoneal paclitaxel to standard intravenous paclitaxel plus S-1 improve survival in patients with gastric cancer and confirmed peritoneal metastasis?
Study Design
This was a multicenter, open-label, randomized phase 3 superiority trial conducted in 9 hospitals in China. Adults with gastric adenocarcinoma and peritoneal metastasis confirmed by laparoscopy were eligible, provided they had no metastases outside the peritoneum and had not received prior systemic therapy for advanced disease.
A total of 246 patients were assessed for eligibility, and 238 were randomized in a 2:1 ratio. The main analysis included 222 patients who received treatment. Patients were assigned to one of two first-line regimens:
1. The IP group received paclitaxel intravenously at 50 mg/m2 plus intraperitoneally at 20 mg/m2 on days 1 and 8 of each 21-day cycle, together with oral S-1 at 80 mg/m2 daily on days 1 through 14.
2. The PS group received the standard comparator regimen of paclitaxel intravenously at 70 mg/m2 on days 1 and 8, plus oral S-1 at 80 mg/m2 daily on days 1 through 14.
The primary endpoint was overall survival. Secondary endpoints included progression-free survival and safety.
Key Results
After a median follow-up of 72.2 months, the trial showed a clear survival advantage for the group that received intraperitoneal paclitaxel.
Median overall survival was 19.4 months in the IP group versus 13.9 months in the PS group. This corresponded to a hazard ratio of 0.67, meaning the risk of death was about 33% lower in the IP group during the study period. The difference was statistically significant.
Progression-free survival also improved. Median progression-free survival was 11.2 months in the IP group compared with 7.2 months in the PS group, with a hazard ratio of 0.72. In practical terms, patients receiving intraperitoneal treatment remained free from disease worsening for a longer period.
Safety findings were 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 that the addition of intraperitoneal paclitaxel did not lead to a major increase in severe toxicity. Importantly, there were no treatment-related deaths in either group.
What the Findings Mean
These results suggest that directly treating the peritoneal cavity can provide a real clinical benefit in a disease that has long had a poor outlook. The study supports the idea that peritoneal metastasis may require a different treatment strategy from metastatic disease elsewhere in the body. Because the peritoneum is partly isolated from the bloodstream, drugs given only intravenously may not reach sufficiently high concentrations at the site of disease. Intraperitoneal administration helps address that problem.
The improvement in overall survival is especially meaningful because it was achieved without a corresponding increase in severe side effects. For patients and clinicians, this matters: a treatment that lengthens life but causes unacceptable toxicity may not be practical, whereas a regimen that improves survival while keeping safety manageable is more likely to be adopted in real-world care.
Clinical Context
Gastric cancer remains a major global health problem, and peritoneal spread is one of the most common and ominous patterns of dissemination. Patients with peritoneal metastasis often cannot benefit from surgery alone, and systemic chemotherapy has limited effectiveness because drug delivery to the peritoneal surfaces is often suboptimal. Over the years, combinations based on fluoropyrimidines and taxanes have become common first-line options in East Asia, but outcomes still leave much room for improvement.
Intraperitoneal paclitaxel is not a new concept, but high-quality randomized phase 3 evidence has been limited. Earlier studies and institutional experiences suggested possible benefit, yet many were smaller, single-center, or nonrandomized. DRAGON-01 provides stronger evidence that this strategy may improve outcomes when used as part of first-line treatment for carefully selected patients with peritoneal-only metastasis.
Important Strengths and Limitations
One major strength of this trial is its randomized design, which reduces the risk that patient characteristics alone explain the outcome difference. The multicenter setting also improves generalizability within the studied population. Long follow-up allowed the investigators to assess survival more fully than in shorter studies.
There are, however, important limitations to keep in mind. The trial was open-label, so both patients and clinicians knew which treatment was given. That can sometimes influence supportive care or assessment of symptoms, although overall survival is an objective endpoint less vulnerable to bias. The study was also conducted in China, where S-1 is widely used and treatment practices may differ from those in other regions. In addition, the findings apply specifically to patients with laparoscopically confirmed peritoneal metastasis and no extra-peritoneal spread; the results may not be directly transferable to patients with liver, lung, or other distant metastases.
Safety and Tolerability
From a practical standpoint, the safety profile is encouraging. Severe adverse events were common enough to require attention, as is typical for combination chemotherapy in advanced gastric cancer, but they were not substantially more frequent in the intraperitoneal arm. The absence of treatment-related deaths suggests that the regimen can be delivered safely in experienced centers.
As with any paclitaxel-based therapy, clinicians still need to monitor for bone marrow suppression, neuropathy, fatigue, nausea, and other chemotherapy-related toxicities. Patients receiving intraperitoneal therapy also require careful procedural support, because intraperitoneal delivery often involves a catheter or access port and specialized nursing and surgical expertise.
Implications for Practice
The study offers an encouraging signal that intraperitoneal chemotherapy may deserve a larger role in first-line management of gastric cancer with peritoneal metastasis. For centers that have the necessary experience and infrastructure, the addition of intraperitoneal paclitaxel could become an important option for selected patients.
At the same time, implementation requires more than enthusiasm. Hospitals need trained teams, catheter management protocols, infection prevention measures, and close follow-up. Patients also need clear counseling about the goals of treatment, possible side effects, and the importance of prompt reporting of abdominal pain, fever, or signs of catheter problems.
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 toxic effects. The findings strengthen the case for intraperitoneal therapy as a promising first-line strategy in this difficult-to-treat subgroup of gastric cancer.
While further studies in broader populations and different health care settings will be important, DRAGON-01 represents a meaningful step forward and may help reshape treatment expectations for patients facing peritoneal metastasis from gastric cancer.