Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer

Abstract

Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

“…2009). Our study shows that the usage of dosages adjusted by UGT1A1 genotype and patients' clinic charatcters caused the lower incidence of severe toxicity compared with 20%-30% showed in some studies (Negoro et al, 1991;Rothenberg et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Rothenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003). It illustrates that pharmacogenetic testing of UGT1A1 is meaningful in clinic.…”

“…But its usage always be limited by its severe side effects especially diarrhea and myelosuppression which are doselimiting toxicities (Negoro et al, 1991;Rothenberg et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Rothenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003). Clinical administration dosage is generally calculated according to the body surface area or weight presently which is the group average dose (Reilly and Workman, 1993).…”

“…Because CPT-11 causes severe diarrhea and neutropenia in 20% to 35% of patients treated (Negoro et al, 1991;Rothenberg, et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Rothenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003), and fatal events (up to 5.3% prevalence) during single-agent irinotecan treatment have been reported (Vanhoefer et al, 2001). We associated these two kind side effects with UGT1A1 genotypes, clinic characters and each other to detect the relationship between them by multivariate logistic analysis We took the sex, age, KPS, number of metastasis, history of chemotherapy, UGT1A1 genotype, dosage, leucopenia, neutropenia, primary cancer and pathological type into risk factors.…”

“…Although it prolongs survival, patients who treated with chemotherapy include irinotecan is often accompanied by unpredictable and sever side effects. It causes severe diarrhea and neutropenia in 20% to 35% of patients treated (Negoro et al, 1991;Rothenberg et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Othenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003). Fatal events (up to 5.3% prevalence) during single-agent irinotecan treatment have been reported (Vanhoefer et al, 2001).…”

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

“…Weekly and every 3-week schedules of irinotecan demonstrate comparable toxicity and efficacy (Rougier et al, 1997;Fusch et al, 2003), but the weekly combination of irinotecan/5-FU shows excessive toxicity (Rothenberg et al, 2001). The FOLFIRI regimen (Douillard et al, 2000) is less toxic, and infusional 5-FU or capecitabine combinations are favoured (Han et al, 2003;Tewes et al, 2003;Bajetta et al, 2004;Jordan et al, 2004).…”