Massive Ascites Mimicking Progressive Disease During Zolbetuximab Treatment in Claudin 18.2-Positive Advanced Gastric Cancer: A Case Report

Gastric cancer, a disease that begins in the lining of the stomach, remains a formidable challenge when it spreads beyond its original site. For decades, doctors have relied on chemotherapy to slow its growth, but in recent years, a new class of treatments has emerged that targets specific proteins on the surface of cancer cells. One such target is a protein called claudin 18.2, which acts like a seal between the cells of the stomach lining. In healthy tissue, this protein helps maintain a tight barrier, but in a specific subset of stomach cancers, it is overproduced. A drug known as zolbetuximab was developed to seek out and bind to this protein, effectively flagging the cancer cells for destruction by the body's immune system. Clinical trials have shown that adding this drug to standard chemotherapy can significantly extend the lives of patients with this specific type of cancer, making it a new standard of care. However, because the drug targets a protein that also exists in normal, healthy stomach cells, there is a risk that it might accidentally damage the healthy tissue, causing unexpected side effects that doctors must learn to recognize and manage.

This story begins with a woman in her forties who was diagnosed with advanced stomach cancer that had already spread to the lining of her abdominal cavity. Her medical team confirmed that her tumor cells were rich in the claudin 18.2 protein, making her an ideal candidate for treatment with zolbetuximab combined with standard chemotherapy. She began the regimen, which involved taking oral medication and receiving intravenous infusions every three weeks. For the first two cycles, the treatment proceeded as planned, but then a troubling sign appeared. A routine scan revealed a massive accumulation of fluid in her abdomen, a condition known as ascites. In the context of advanced cancer, such a sudden and severe buildup of fluid is almost always a warning sign that the disease is growing out of control, a phenomenon doctors call progressive disease. The natural instinct would be to stop the current treatment immediately, assuming it had failed, and switch to a different approach.

Yet, the medical team at the National Cancer Centre in Japan noticed something that did not fit the pattern of a worsening cancer. While the fluid in her belly was increasing, her blood tests told a different story. The levels of tumor markers, which are substances released by cancer cells that doctors use to track the disease, were dropping sharply. Furthermore, the patient was suffering from severe loss of appetite and signs of malnutrition, suggesting that her body was struggling to absorb nutrients rather than being overwhelmed by a growing tumor. The doctors hypothesized that the fluid buildup was not caused by the cancer spreading, but rather by the treatment itself. They suspected that the zolbetuximab, while attacking the cancer, had also temporarily damaged the barrier of her healthy stomach lining. This damage likely allowed protein to leak out of her blood vessels and into her abdominal cavity, a condition known as protein-losing gastroenteropathy. The loss of protein caused her body to retain fluid, creating the massive ascites that had initially looked like a sign of failure.

Instead of abandoning the treatment, the team made a calculated decision to pause the chemotherapy for a short time while providing supportive care to help her body recover. They used diuretics to help her body eliminate the excess fluid and focused on managing her nutrition. The result was rapid and striking. Within two weeks, the fluid in her abdomen began to recede, and her symptoms improved significantly. This quick recovery suggested that the fluid buildup was a reversible reaction to the drug, rather than a sign that the cancer was winning. With the immediate crisis resolved, the team resumed the chemotherapy. The patient continued the treatment for eight more cycles, and the cancer responded beautifully. Scans showed that the spread of the disease within her abdomen had shrunk, and the fluid had largely disappeared.

This improvement opened a door that is rarely available to patients with such advanced disease. The team performed a second surgical exploration to look inside her abdomen, finding no evidence of the cancer cells that had been there before. The fluid was clear of cancer cells, and the spread of the disease had vanished. This allowed the surgeons to perform a radical operation to remove the entire stomach and the surrounding lymph nodes, a procedure known as conversion surgery. The pathology report after the surgery showed that the cancer had retreated significantly, leaving behind only a small area of change that corresponded to the treatment's effect. The patient recovered from the surgery and was discharged. One month after the surgery, the patient remained free of any evident recurrence.

The significance of this case lies in the lesson it offers to other doctors treating similar patients. When a patient on zolbetuximab develops sudden, severe fluid in the abdomen, it is easy to mistake it for the cancer getting worse. If doctors make that mistake, they might stop a treatment that is actually working, depriving the patient of a chance at a cure. This report suggests that such fluid buildup can sometimes be a side effect of the drug damaging the stomach lining, causing protein loss, rather than a sign of tumor growth. By recognizing this pattern and pausing treatment briefly to let the body heal, doctors can avoid stopping effective therapy too soon. While the diagnosis in this specific case was made based on clinical observation and the patient's rapid response to supportive care, rather than through invasive testing of the fluid itself, the favorable outcome supports the idea that the early massive ascites did not represent irreversible disease progression. This case adds a crucial piece of knowledge to the growing understanding of how to safely and effectively use this new class of cancer-fighting drugs.