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Annals of Oncology 14:ii17-ii23, 2003
© 2003 European Society for Medical Oncology

Irinotecan in metastatic colorectal cancer: dose intensification and combination with new agents, including biological response modifiers

M. Ducreux1, C.-H. Köhne2,+, G. K. Schwartz3 and U. Vanhoefer4

1 Institut Gustave Roussy, Villejuif, France; 2 University Clinic of Carl-Gustav, Technical University of Dresden, Germany; 3 Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 4 West German Cancer Center, University of Essen Medical School, Essen, Germany

Abstract

Phase I/II studies suggest that the combination of irinotecan with capecitabine is feasible and has promising activity. Diarrhea and neutropenia are dose limiting. Overall response rates (RRs) in the 40% to 60% range are seen from preliminary data. Work in progress is assessing the combination of irinotecan with UFT/leucovorin (LV). The use of irinotecan together with raltitrexed is also being investigated, as is its combination with oxaliplatin. Two phase II studies of irinotecan plus oxaliplatin in second-line patients report median survivals of 11–12 months. It seems possible to safely escalate the dose of single-agent irinotecan to 500 mg/m2 in patients showing good tolerance of the drug. Irinotecan can be used in combination with LV5FU2 at doses up to 260 mg/m2, especially if only one bolus of 5-fluorouracil (5-FU) is given. Control of tumor growth is achieved in 90% of patients. Preliminary data suggest that regimens based on 5-FU/LV and irinotecan can safely be combined with the anti-epidermal growth factor receptor (EGFR) antibody cetuximab. In patients with EGFR-positive tumors, this may prove an effective means of increasing response rate or combating treatment resistance. Following evidence that COX-2 inhibition can slow progression in familial adenomatous polyposis, celecoxib is to be studied in metastatic colorectal cancer (CRC). In vitro, the cyclin-dependent kinase inhibitor flavopiridol enhances the induction of apoptosis by chemotherapy. Clinically, it can safely be administered with irinotecan, and studies in CRC are planned.


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