Irinotecan (CPT-11) in Patients with Advanced Colon Carcinoma Relapsing after 5-Fluorouracil-Leucovorin Combination

Abstract

The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m² in patients with a PS 70–80 (group A), and 350 mg/m² for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS ≧ 90 or ≤ 80 (p = 0.925), or between those who received a mean dose of CPT-11 ≧300 or ≤300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m² every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.

The Irinotecan/5-Fluorouracil Combination Induces Apoptosis and Enhances Manganese Superoxide Dismutase Activity in HT-29 Human Colon Carcinoma Cells

“…5-FU is a fluoropyrimidine that demonstrated a dual mechanism of action: brief exposure to 5-FU induced an RNA-directed toxicity, while TS inhibition and DNAdirected toxicity occurred with prolonged exposure [7,8]. CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin; irinotecan; Camptosar ® ) is a topoisomerase-I-inhibiting agent that has shown antitumor activity in patients with colon cancer when administered alone as first-line therapy or as second-line therapy after 5-FU failure [9,10]. CPT-11 is enzymatically converted by carboxylesterases to its most active metabolite, SN-38 (7-ethyl-10-hydroxyl-camptothecin) [11].…”

Intestinal Permeability in the Assessment of Intestinal Toxicity of Cytotoxic Agents

“…irinotecan, it is the limiting toxicity [1] . Any part of the gastrointestinal tract may be affected.…”

Combined Systemic Chronotherapy and Hepatic Artery Infusion for the Treatment of Metastatic Colorectal Cancer Confined to the Liver

“…However, these protocols carry some degree of morbidity with moderate side effects relating especially to L-OHP as grade 3/4 neutropenia or neurotoxicity occurring in 41.7 and 68% of the patients, respectively [19,21] . The high reported response rate mentioned above was very disappointing when treating patients who were refractory to 5FU/folinic acid and irinotecan amounting to between 15 and 25% [22,23] . Our trial demonstrated a 40% partial response rate and stable disease for at least 4 months in 13% of the patients.…”