Takeda, Y., Kobayashi, K., Akivama, Y., Soma, T., Handa, S., Kudoh, S., & Kudo, K. (2001). Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. International Journal of Cancer, 92(2), 269–275.

To evaluate the use of oral alkalization (OA) with control of defecation (CD)

• Patients were given OA, consisting of 0.5 g NaHCO₃ (sodium bicarbonate) and 0.5 g magnesium oxide, after meals and at bedtime with basic water (pH > 7.2) continuously for a total of 1,500-2,000 mL/d and 100 mg oral ursodeoxycholic acid 100 mg po 1–4 times daily after meals.
• For CD (administering laxative treatment to avoid long contact time of irinotecan metabolite with bowel mucosa), patients were given up to 4 g per day of magnesium oxide and 2 L per day of excess basic water.
• If patients experienced watery diarrhea with OA and CD, magnesium oxide was discontinued until symptom resolution.

• The study evaluated Japanese patients with small cell lung cancer or nonsmall cell lung cancer.
• Group B consisted of 37 consecutive patients from three ongoing, prospective, phase I/II studies receiving irinotecan in combination with cisplatin in the presence of OA and CD.
• Group A consisted of 32 control subjects without OA and CD who were matched to the background characteristics of the case patients treated with irinotecan and cisplatin.

The study was conducted at a single institution.

This was a case-control study.

• Intraluminal pH, hematologic toxicity, and nonhemotologic toxicity were evaluated.
• Gastrointestinal (GI) evaluation included recording appetite loss, nausea and vomiting, constipation, delayed diarrhea, and amount of loperamide used.
• Dose intensity and response were recorded.
• Use of loperamide was recorded. Patients received 2 mg loperamide on demand after every diarrheal episode. When this approach did not succeed, patients were managed with 2 mg of loperamide every 4 hours routinely until free of diarrhea for 12 hours.

• European Cooperative Oncology Group (ECOG) Common Toxicity Criteria (CTC) were measured.
• The OA and CD group (group B) had the following results.
  • Higher stool pH (p < 0.0001)
  • Reduced incidence of delayed diarrhea at grade 2 or higher (group A = 32.3%, group B = 9.4%, p = 0.005)
  • Nausea (p = 0.0001)
  • Vomiting (p = 0.001)
  • Myelotoxicity (p = 0.03)
  • Lymphocytopenia (p = 0.034)
  • Dose intensification (from 34.6 to 39.9 mg/m² per week [p < 0.001])
  • Tumor response rate of 59.3% versus 38.5% in group A (p = 0.173).
• Duration of delayed diarrhea was 2.8 times longer in group A (p < 0.0001).
• Loperamide use was greater in group A (p = 0.003).

Patient response rates did not indicate that OA and CD compromised the clinical efficacy of irinotecan and cisplatin therapy. Although a reduced amount of irinotecan and SN-38 may be circulated enterohepatically, the increased dose intensity conferred by OA and CD resulted in maintenance of the same degree of clinical efficacy.

OA and CD appeared to be useful in preventing the dose-limiting side effects of irinotecan, primarily nausea, vomiting, granulocytopenia, and delayed diarrhea.