Oral Alkalization

Oral Alkalization

PEP Topic 
Chemotherapy-Induced Diarrhea
Description 

SN-38, the active metabolite of irinotecan, has absorption characteristics of weakly basic drugs. Alkalization of the intestinal lumen may reduce reabsorption of SN-38 and its attendant side effects. This approach has been examined related to the topic of diarrhea.

Effectiveness Not Established

Research Evidence Summaries

Maeda, Y., Ohune, T., Nakamura, M., Yamasaki, M., Kiribayashi, Y., & Murakami, T. (2004). Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin) in cancer patients. Oncology Reports, 12(3), 581–585.

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Study Purpose:

To examine the effectiveness of two interventions, AST-120 and oral alkalization, to ameliorate diarrhea after treatment with irinotecan

Intervention Characteristics/Basic Study Process:

  • Patients with varying cancers who were receiving irinotecan were given AST-120, oral alkalization, or nothing (control).
  • AST-120 (Kremezin™) is an oral adsorbent made of activated carbon. Patients received 2 g at the start of irinotecan infusion, immediately after irinotecan infusion, and three hours after irinotecan infusion.
  • Oral alkalization, consisting of 2 g NaHCO3 (sodium bicarbonate), 2 g magnesium oxide, and 300 mg ursodexycholic acid, was given before irinotecan and then daily for three days after irinotecan administration.

Sample Characteristics:

The study reported on 13 Japanese patients with cancer receiving 60–100 mg/m2 irinotecan every 1–2 weeks, alone or as part of a combination regimen. The control group consisted of 7 patients, the AST-120 group consisted of 4 patients, and the oral alkalization group consisted of 4 patients. One patient in each of the two intervention groups served as his or her own control, having received prior irinotecan with no prophylaxis.

Study Design:

This was a nonrandomized trial.

Measurement Instruments/Methods:

Patients recorded the number of bowel movements but not the volume.

Results:

  • Oral alkalization appeared to be effective in ameliorating diarrhea, although the efficiency did not reach a significant difference (level of significance not indicated).
  • AST-120 significantly decreased the maximum number of daily bowel movements during irinotecan treatments as compared with no prophylaxis (p < 0.05).

Limitations:

  • This was a small study with only 13 patients.
  • One patient in the AST-120 group and one patient in the oral alkalization group acted as his or her own control. Only three other patients were in each interventional treatment group.

Nursing Implications:

Although further study is necessary regarding the effect of oral AST-120 on plasma concentrations of irinotecan-related compounds, it is speculated that the absorption of irinotecan or SN-38 from the intestinal lumen is small, if any, and the remaining irinotecan-related compounds in the intestinal lumen cause diffuse mucosal damage in irinotecan treatments.

Moreno, V.V., Vidal, J.B., Alemany, H.M., Salvia, A.S., Serentill, M.L., Montero, I.C., . . . Padró, J.G. (2006). Prevention of irinotecan associated diarrhea by intestinal alkalization. A pilot study in gastrointestinal cancer patients. Clinical and Translational Oncology, 8, 208–212.

doi: 10.1007/s12094-006-0012-1
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Intervention Characteristics/Basic Study Process:

Two grams of powdered NaHCO3 diluted in 250 ml water was sipped during the days of irinotecan administration, starting in the morning. Other fluids were taken ad lib.

Sample Characteristics:

  • N = 24
  • KEY DISEASE CHARACTERISTICS: Patients with gastrointestinal carcinoma 
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients receiving varying irinotecan-based regimens 

Setting:

  • SITE: Multi-site
  • LOCATION: Four Spanish community practice settings

Study Design:

  • Experimental, interventional, prospective study
    • No control

Measurement Instruments/Methods:

  • Diarrhea grade, although no mention of which grading scale was used

Results:

Four of 24 patients (16%) had grade III–IV diarrhea (8 had prior pelvic radiation therapy, a risk factor associated with diarrhea). Comparison was made to incidence of grade II–IV diarrhea in previous colorectal cancer studies. The researchers’ conclusion was that intestinal alkalization may be effective in preventing diarrhea with patients with gastrointestinal cancer receiving irinotecan.


 

Limitations:

  • Uncontrolled trial
  • Small numbers

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.

doi: 10.1002/1097-0215(200102)9999:9999<::AID-IJC1179>3.0.CO;2-3
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Study Purpose:

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

Intervention Characteristics/Basic Study Process:

  • 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.

Sample Characteristics:

  • 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.

Setting:

The study was conducted at a single institution.

Study Design:

This was a case-control study.

Measurement Instruments/Methods:

  • 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.

Results:

  • 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).

Conclusions:

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.

Nursing Implications:

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


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