Two different schedules of irinotecan (CPT-11) in patients with advanced colorectal carcinoma relapsing after a 5-fluorouracil and leucovorin combination. A randomized study

Abstract

. The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.

A Pilot Human Evaluation of a Formulation of Irinotecan and Hyaluronic Acid in 5-Fluorouracil-Refractory Metastatic Colorectal Cancer Patients

“…In this mixed patient population, including 3 patients who had previously received oxaliplatin chemotherapy, responses were seen in 2 of the 12 patients (17%), and stable disease in a further 6 patients (50%), suggesting that formulating irinotecan with HA did not compromise treatment efficacy. These data are comparable with historical results that cite the expected response rate in a similar patient population of 5-22% [5,7,8] .…”

“…The median survival was 16.6 months versus an expected 7-10.8 months and the progression-free survival was 6.2 months versus an expected 2.6-4.5 months [4,5,8,13,49] . When compared to the historical data, the median number of cycles delivered for 350 mg/m 2 of irinotecan every 3 weeks is normally 2-2.5 [50,51], where the primary reason for the limited number of cycles is withdrawal due to treatment toxicity or progressive disease.…”

“…Unfortunately, toxicity from irinotecan is significant and unpredictable [12] , with the primary dose-limiting toxicities being diarrhea and neutropenia. Grade III/IV diarrhea occurs in 16-41% of patients receiving 350 mg/m 2 of irinotecan on a 3-weekly schedule [4,5,[7][8][9][13][14][15] and, despite the aggressive use of loperamide, severe diarrhea was reported in 31 and 30% of patients in two reported studies [10,11] . Grade III/IV neutropenia is reported to occur in 14-47% of patients [4,[7][8][9][13][14][15][16] and grade III/IV nausea and vomiting in 11-30% [4,5,[7][8][9][13][14][15] .…”

“…with response rates of approximately 14% in 5-fluorouracil (5-FU)-refractory patients [8][9][10] , but lower responses are often observed in patients who have received prior oxaliplatin [11] . Unfortunately, toxicity from irinotecan is significant and unpredictable [12] , with the primary dose-limiting toxicities being diarrhea and neutropenia.…”

In vitro detection of cross-resistant and non-cross-resistant agents with fluorouracil for patients with colorectal cancer

“…Only a few articles have dealt with second-line chemotherapy after 5-FU failure, although it is a high priority, [11][12][13] and there have been few comparative studies of second-line chemotherapies, although first-line chemotherapy with 5-FU/ leucovorin has proven its efficacy in several comparative studies. 2,14 Only irinotecan has been considered as a potential agent for second-line chemotherapy compared with supportive care after fluorouracil failure. However, it has not, to date, been proven comparatively whether irinotecan is the best cytotoxic agent.…”