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.
BACKGROUND
Irinotecan is an established therapeutic option in colorectal cancer. An essential side effect of irinotecan treatment is the induction of severe WHO grade 3-4 delayed diarrhea in up to 25% of treated patients. The aim of the study is the prevention of delayed diarrhea with cholestyramine/levofloxacin.


METHODS
Fifty-one patients with a mean age of 64 years (range: 41-81 years) with metastatic colorectal cancer in second-line treatment were included. A cycle corresponds to 4 applications of irinotecan 250 mg/m2, every 2 weeks, then a break of 2 weeks.


RESULTS
After 1 treatment cycle 12% of patients achieved a partial response, 59% had stable disease and 29% progressive disease. Twenty-two patients received a second or more cycles to a total of 379 applications. Forty patients did not develop diarrhea whereas 11 patients had WHO 1-2 diarrhea after at least 1 application of chemotherapy. Diarrhea WHO 3 occurred in only 1 patient (2%) whereas severe diarrhea WHO 4 did not occur.


CONCLUSIONS
The combination of cholestyramine/levofloxacin is a promising option for the prevention of delayed diarrhea caused by irinotecan. This prophylactic regime may help in future to escalate the dose of irinotecan as a monotherapy or in combination protocols.
Flieger
Dimitri
D
I. Medizinische Klinik, GP-Klinikum Russelsheim, Russelsheim, Germany. d.flieger@uni-bonn.de
Klassert
Christine
C
Hainke
Sabine
S
Keller
Ralf
R
Kleinschmidt
Rolf
R
Fischbach
Wolfgang
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000930:Antidiarrheals / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002792:Cholestyramine Resin / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000627:therapeutic use*; D013997:Time Factors
D000930:Antidiarrheals; D002792:Cholestyramine Resin; D064704:Levofloxacin; D000077146:Irinotecan; D015242:Ofloxacin; D002166:Camptothecin