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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

Jean-Luc Raoul, Jean-Luc Van Laethem, Marc Peeters UGent, Catherine Brezault, Fares Husseini, Laurent Cals, Johannes Nippgen, Anja-Helena Loos and Philippe Rougier (2009) BMC CANCER. 9.
abstract
Background: 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. Methods: 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(2) initial dose and 250 mg/m(2)/week thereafter) and every 2 weeks irinotecan (180 mg/m(2)), FA (400 mg/m(2)) and 5-FU (either low dose [LD], 300 mg/m(2) bolus plus 2,000 mg/m(2) 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m(2) bolus plus 2,400 mg/m(2); n = 45). Results: 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. Conclusion: 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
II TRIAL, FLUOROURACIL, KRAS STATUS, PLUS IRINOTECAN, CLINICAL-RELEVANCE, 1ST-LINE TREATMENT, LIVER METASTASES, CHEMOTHERAPY, OXALIPLATIN, GROWTH-FACTOR RECEPTOR
journal title
BMC CANCER
BMC Cancer
volume
9
article_number
112
pages
12 pages
Web of Science type
Article
Web of Science id
000266726100001
JCR category
ONCOLOGY
JCR impact factor
2.736 (2009)
JCR rank
71/163 (2009)
JCR quartile
2 (2009)
ISSN
1471-2407
DOI
10.1186/1471-2407-9-112
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
687062
handle
http://hdl.handle.net/1854/LU-687062
date created
2009-06-10 09:58:10
date last changed
2012-10-31 09:51:58
@article{687062,
  abstract     = {Background: 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. 
Methods: 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(2) initial dose and 250 mg/m(2)/week thereafter) and every 2 weeks irinotecan (180 mg/m(2)), FA (400 mg/m(2)) and 5-FU (either low dose [LD], 300 mg/m(2) bolus plus 2,000 mg/m(2) 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m(2) bolus plus 2,400 mg/m(2); n = 45). 
Results: 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. 
Conclusion: 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.},
  articleno    = {112},
  author       = {Raoul, Jean-Luc and Van Laethem, Jean-Luc and Peeters, Marc and Brezault, Catherine and Husseini, Fares and Cals, Laurent and Nippgen, Johannes and Loos, Anja-Helena and Rougier, Philippe},
  issn         = {1471-2407},
  journal      = {BMC CANCER},
  keyword      = {II TRIAL,FLUOROURACIL,KRAS STATUS,PLUS IRINOTECAN,CLINICAL-RELEVANCE,1ST-LINE TREATMENT,LIVER METASTASES,CHEMOTHERAPY,OXALIPLATIN,GROWTH-FACTOR RECEPTOR},
  language     = {eng},
  pages        = {12},
  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},
  url          = {http://dx.doi.org/10.1186/1471-2407-9-112},
  volume       = {9},
  year         = {2009},
}

Chicago
Raoul, Jean-Luc, Jean-Luc Van Laethem, Marc Peeters, Catherine Brezault, Fares Husseini, Laurent Cals, Johannes Nippgen, Anja-Helena Loos, and Philippe Rougier. 2009. “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 9.
APA
Raoul, J.-L., Van Laethem, J.-L., Peeters, M., Brezault, C., Husseini, F., Cals, L., Nippgen, J., et al. (2009). 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, 9.
Vancouver
1.
Raoul J-L, Van Laethem J-L, Peeters M, Brezault C, Husseini F, Cals L, et al. 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. 2009;9.
MLA
Raoul, Jean-Luc, Jean-Luc Van Laethem, Marc Peeters, et al. “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 9 (2009): n. pag. Print.