Irinotecan in metastatic colorectal cancer: Dose intensification and combination with new agents, including biological response modifiers Conference Paper
| Authors: | Ducreux, M.; Köhne, C. H.; Schwartz, G. K.; Vanhoefer, U. |
| Title: | Irinotecan in metastatic colorectal cancer: Dose intensification and combination with new agents, including biological response modifiers |
| Conference Title: | Clinical Investigators Update Meeting on Gastrointestinal Cancer |
| 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. |
| Keywords: | cancer survival; treatment outcome; clinical trial; drug activity; neutropenia; erlotinib; fluorouracil; cancer combination chemotherapy; cancer growth; diarrhea; dose response; drug safety; capecitabine; drug megadose; colorectal cancer; metastasis; apoptosis; enzyme inhibition; nausea; antineoplastic combined chemotherapy protocols; drug administration schedule; antineoplastic agents, phytogenic; camptothecin; membrane proteins; in vitro study; cetuximab; docetaxel; irinotecan; asthenia; febrile neutropenia; colorectal neoplasms; cancer inhibition; gastrointestinal toxicity; antibodies, monoclonal; enzyme inhibitors; celecoxib; cyclooxygenase 2 inhibitor; folinic acid; cyclooxygenase 2; gefitinib; flavonoids; flavopiridol; piperidines; loperamide; oxaliplatin; drug dose regimen; deoxycytidine; quinazolines; cyclin dependent kinase inhibitor; organoplatinum compounds; leucovorin; drug tolerance; clinical trials; isoenzymes; adenomatous polyp; thiophenes; raltitrexed; uft; biological response modifiers; prostaglandin-endoperoxide synthases; humans; human; priority journal; article |
| Journal Title | Annals of Oncology |
| Volume: | 14 |
| Issue: | Suppl.2 |
| Conference Dates: | 2002 Apr 20 |
| Conference Location: | Cagliari, Italy |
| ISBN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2003-06-01 |
| Start Page: | ii17 |
| End Page: | ii23 |
| Language: | English |
| PUBMED: | 12810453 |
| PROVIDER: | scopus |
| DOI: | 10.1093/annonc/mdg724 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
