Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study
<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU)...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-04-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/112 |
| _version_ | 1818035731086442496 |
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| author | Cals Laurent Husseini Fares Brezault Catherine Peeters Marc Van Laethem Jean-Luc Raoul Jean-Luc Nippgen Johannes Loos Anja-Helena Rougier Philippe |
| author_facet | Cals Laurent Husseini Fares Brezault Catherine Peeters Marc Van Laethem Jean-Luc Raoul Jean-Luc Nippgen Johannes Loos Anja-Helena Rougier Philippe |
| author_sort | Cals Laurent |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer.</p> <p>Methods</p> <p>The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m<sup>2 </sup>initial dose and 250 mg/m<sup>2</sup>/week thereafter) and every 2 weeks irinotecan (180 mg/m<sup>2</sup>), FA (400 mg/m<sup>2</sup>) and 5-FU (either low dose [LD], 300 mg/m<sup>2 </sup>bolus plus 2,000 mg/m<sup>2 </sup>46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m<sup>2 </sup>bolus plus 2,400 mg/m<sup>2</sup>; n = 45).</p> <p>Results</p> <p>Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS.</p> <p>Conclusion</p> <p>The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.</p> |
| first_indexed | 2024-12-10T06:59:43Z |
| format | Article |
| id | doaj.art-20654d7b6c954d40bd470d6e79ef16a0 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T06:59:43Z |
| publishDate | 2009-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-20654d7b6c954d40bd470d6e79ef16a02022-12-22T01:58:21ZengBMCBMC Cancer1471-24072009-04-019111210.1186/1471-2407-9-112Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II studyCals LaurentHusseini FaresBrezault CatherinePeeters MarcVan Laethem Jean-LucRaoul Jean-LucNippgen JohannesLoos Anja-HelenaRougier Philippe<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer.</p> <p>Methods</p> <p>The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m<sup>2 </sup>initial dose and 250 mg/m<sup>2</sup>/week thereafter) and every 2 weeks irinotecan (180 mg/m<sup>2</sup>), FA (400 mg/m<sup>2</sup>) and 5-FU (either low dose [LD], 300 mg/m<sup>2 </sup>bolus plus 2,000 mg/m<sup>2 </sup>46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m<sup>2 </sup>bolus plus 2,400 mg/m<sup>2</sup>; n = 45).</p> <p>Results</p> <p>Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS.</p> <p>Conclusion</p> <p>The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.</p>http://www.biomedcentral.com/1471-2407/9/112 |
| spellingShingle | Cals Laurent Husseini Fares Brezault Catherine Peeters Marc Van Laethem Jean-Luc Raoul Jean-Luc Nippgen Johannes Loos Anja-Helena Rougier Philippe Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study BMC Cancer |
| title | Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study |
| title_full | Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study |
| title_fullStr | Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study |
| title_full_unstemmed | Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study |
| title_short | Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study |
| title_sort | cetuximab in combination with irinotecan 5 fluorouracil folinic acid folfiri in the initial treatment of metastatic colorectal cancer a multicentre two part phase i ii study |
| url | http://www.biomedcentral.com/1471-2407/9/112 |
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