Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

Abstract

CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study

“…None of the differences in response rate between the groups were statistically significant. It is worth mentioning that the response rate observed in Group A was unusually low, and less than that seen in published studies of similar populations of patients treated with the same schedule (Rougier et al, 1997;Van Cutsem et al, 1999). This may be due to changes in first-line treatment that have occurred in recent years; compared with patients treated in earlier studies, those in the present study may have been more heavily pretreated with 5-FU and oxaliplatin in the first-line setting, thus making them more Optimisation of irinotecan dosing E Van Cutsem et al chemotherapy resistant.…”

“…Phase II trials have demonstrated objective response rates of 16 -27% in pretreated patients, with stabilisation of disease in a further 40 -60% of patients (Rougier et al, 1997;Van Cutsem et al, 1999). Median overall survival rates of up to 10 months are achievable when irinotecan is used in relapsed/refractory colorectal cancer (Shimada et al, 1993;Rothenberg et al, 1996Rothenberg et al, , 1999Pitot et al, 1997;Rougier et al, 1997;Van Cutsem et al, 1999).…”

“…Phase II trials have demonstrated objective response rates of 16 -27% in pretreated patients, with stabilisation of disease in a further 40 -60% of patients (Rougier et al, 1997;Van Cutsem et al, 1999). Median overall survival rates of up to 10 months are achievable when irinotecan is used in relapsed/refractory colorectal cancer (Shimada et al, 1993;Rothenberg et al, 1996Rothenberg et al, , 1999Pitot et al, 1997;Rougier et al, 1997;Van Cutsem et al, 1999). Two European phase III trials investigating the efficacy and safety of irinotecan, following 5-FU failure in advanced colorectal cancer, have demonstrated significant improvements in survival compared with best supportive care and 5-FU (Cunningham et al, 1998;Rougier et al, 1998).…”

Minimal hepatic toxicity of Onyx-015: spatial restriction of coxsackie-adenoviral receptor in normal liver

“…Despite the recent introduction of new cytotoxic agents and targeted therapies, less than 10% of patients are alive at 5 years. [1][2][3] New approaches are needed to treat patients with metastatic colorectal cancer. Oncolytic viruses have been engineered to exploit mutations in malignant cells and can destroy tumors by cytolytic and immune-based mechanisms that are distinct from the cytotoxic mechanisms of chemotherapeutic agents.…”

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).…”