Cisplatin is known for causing significant gastrointestinal toxicity, including severe diarrhea, which impacts patients' quality of life. Notably, up to 67% of patients suffer from diarrhea during their treatment course. Serotonin (5-hydroxytryptamine, 5HT) emerges as a critical player in the mechanism of cisplatin-induced diarrhea. Cisplatin tends to increase the release of serotonin from the enterochromaffin cells in the gut, which can then bind to 5-HT3 receptors on the afferent nerves, leading to enhanced gut motility and secretion, culminating in diarrhea. Moreover, increased serotonin levels may contribute to the inflammatory response and aggravate gut permeability, further intensifying diarrhea symptoms. While the study discussed the use of ondansetron to inhibit the cisplatin-induced release of 5-HT from the gut and prevent emesis, it did not address any treatments specific to diarrhea. [1]
Though not specific to cisplatin, a consensus statement by the Canadian Working Group on chemotherapy-induced diarrhea provides recommendations on the prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer. Effective management of chemotherapy-induced diarrhea involves prompt intervention with bowel rest, hydration, and electrolyte replacement. Patients should be hospitalized if they show dehydration, fever, neutropenia, or severe nausea and vomiting. Dietary modifications are crucial, including the avoidance of dairy, high-fat foods, caffeine, and alcohol, while increasing oral fluid intake. First-line treatment typically involves loperamide or diphenoxylate. The recommended dose of loperamide is 4 mg initially, followed by 2 mg after each episode of diarrhea, up to a maximum of 16 mg daily. For intractable grade 1 or 2 diarrhea or de novo grade 3 or 4 diarrhea, octreotide is recommended, starting at 100 to 150 mcg subcutaneously three times daily, with the possibility of dose escalation in 50 mcg increments. Octreotide should be discontinued 24 hours after diarrhea resolves. Hospitalized patients should receive intravenous fluids, electrolyte correction, and antibiotics as needed. [2]
Similar to the recommendation provided in the Canadian consensus statement, review articles also refer to loperamide as the first line of defense for the management of chemotherapy-induced diarrhea. If diarrhea continues for more than 24 hours, high-dose loperamide (2 mg every 2 hours) is a recognized treatment option along with starting oral antibiotics to prevent infectious complications. If diarrhea persists beyond 48 hours despite high-dose loperamide, the medication should be discontinued, and second-line treatments such as subcutaneous octreotide (100-150 mcg), tincture of 10 mg/mL opium (10-15 drops in water orally every 3-4 hrs), or oral budesonide (9 mg by mouth daily, or 3 mg by mouth 3 times daily) should be considered. It was also highlighted that while the exact cause of chemotherapy-induced diarrhea is not fully understood, it is thought to involve a complex process that disrupts the balance between fluid absorption and secretion in the gastrointestinal tract. Other factors such as diet, medications, and infections may also contribute to diarrhea in cancer patients. [2], [3], [4]