IRINOTECAN (CPT-11) HIGH-DOSE ESCALATION USING INTENSIVE HIGH-DOSE LOPERAMIDE TO CONTROL DIARRHEA

Background: Diarrhea is a serious side effect that may prevent the adm inistration of high doses of the antitumor drug Irinotecan (CPT-11). P urpose: Intensive, high-dose loperamide was used in an attempt to cont rol or downstage CPT-11-induced diarrhea and thus permit the use of hi gher dose intensities of CPT-11. Methods: Twenty-three patients with v arious cancers were treated with doses of CPT-11 ranging from 400 to 6 00 mg/m(2), administered as a 30-minute intravenous infusion every 3 w eeks. Starting 8 hours or more after the administration of CPT-11, any episode of diarrhea was treated with 2 mg of loperamide taken every 2 hours. Patients stopped taking loperamide only after a 12-hour diarrh ea-free period. If diarrhea was not controlled after 3 consecutive day s of nonstop loperamide intake, or if the patient was dehydrated, lope ramide was stopped and the patient was hospitalized for intravenous fl uids. If blood or mucus were found in the stools at any time during di arrhea, loperamide was stopped and the patient was hospitalized. Resul ts: Seventeen of 23 patients had diarrhea while on CPT-11 treatment. E ighty-two CPT-11 cycles were administered to these 17 patients, and di arrhea occurred in 49 of these cycles, at a median time-to-onset of 6 days after CPT-11 administration. The loperamide protocol was followed in 46 of the 49 episodes of diarrhea, with 21 capsules of loperamide the median number being taken (range, 5-72). Only one patient was hosp italized for failure to respond to loperamide, and no major toxicity w as associated with loperamide use. Fourteen of the 17 patients who exp erienced diarrhea were rechallenged with CPT-11 three or more times, a nd seven patients six or more times. Conclusions: High-dose loperamide controlled diarrhea in patients receiving CPT-11 and allowed administ ration of higher doses of,CPT-ll. Implications: The effectiveness of C PT-11 might be increased by higher dose intensities, which can be made tolerable by control of diarrhea with loperamide.