Flieger, D., Klassert, C., Hainke, S., Keller, R., Kleinschmidt, R., & Fischback, W. (2007). Phase II clinical trial for prevention of delayed diarrhea with cholestyramine/levofloxacin in the second-line treatment with irinotecan biweekly in patients with metastatic colorectal carcinoma. Oncology, 72(1–2), 10–16.

DOI Link

Intervention Characteristics/Basic Study Process

Patients receiving 250 mg/m2 IV irinotecan over 90 minutes every two weeks were given 500 mg levofloxacin tablets once at 8 pm and 4 g cholestyramine three times per day (not together with other medications) beginning the day before chemotherapy to day +1. Patients with acute cholinergic syndrome, abdominal cramping, and early diarrhea, were given 0.25-1 mg IV atropine. Patients experiencing delayed diarrhea were offered loperaminde.

Sample Characteristics

  • The study reported on 51 patients with metastatic colorectal cancer (CRC) in second-line treatment.
  • Mean age was 64 with a range of 41–81.
  • Patients had not received prior irinotecan therapy and were refractory or resistant to 5-fluorouracil (5-FU).

Study Design

This was a phase II trial.

Measurement Instruments/Methods

  • Patients recorded diarrhea incidence and severity in diaries following each chemotherapy dose.
  • Diarrhea severity was measured using World Health Organization (WHO) grading.

Results

  • Forty patients (78%) did not develop diarrhea, 11 patients (22%) reported WHO grade 1–2 diarrhea, and only one patient (2%) reported WHO grade 3 diarrhea.
  • No patients reported grade 4 diarrhea. 
  • Reported incidence of diarrhea without prophylaxis in the literature is up to 40%.

Limitations

  • The study sample was small.
  • This was a phase II study.
  • Investigators did not conduct pharmacokinetic analyses of the active metabolites SN-38 and SN-38G in plasma.
  • No information was provided on the effect of cholestyramine on the efficacy of irinotecan efficacy. If cholestyramine decreases the effects of irinotecan, this could account for a decreased incidence of diarrhea.

Nursing Implications

Combination cholestyramine and levofloxacin is a promising option for prevention of delayed diarrhea caused by irinotecan and may help to escalate the dose of irinotecan in the future.