We first consider Xeliri and the Erbitux with Xeliri.
Currently, there are seven active and approved chemotherapy drugs for patients with metastatic colorectal cancer: 5-FU, capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, and panitumumab. Among the best studied ways of putting some of these drugs together are the regimen Folfox and Folfiri. Three randomized studies demonstrated improved response rates, progression-free survival (PFS), and OS when irinotecan or oxaliplatin was combined with 5-FU-leucovorin. Since the publication of these studies, the use of either FOLFOX or FOLFIRI is considered acceptable for first-line treatment of patients with metastatic colorectal cancer.Avastin is also approved with 5FU containing regimens for first line.
The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offers the advantages of oral administration. The epidermal growth factor receptor antibody cetuximab induces synergistic antitumor activity when combined with chemotherapy. In pretreated patients, cetuximab can restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Several phase I/II trials have investigated the combination of cetuximab with irinotecan-based or oxaliplatin-based chemotherapy for the first-line treatment of mCRC. These combinations have been proven to be safe and have provided promising efficacy data.
Is continuation of Xeliri justified with the addition of cetuximab in second line, as would the continuation of irinotecan alone be with the additioan of Cetuximab?
Cetuximab is approved for use, in combination with irinotecan, for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. However, Xeliri continued in 2nd line with the addtition of cetuximab has not been studied and is investigational.
Colucci G, Gebbia V, Paoletti G, et al.: Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 23 (22): 4866-75, 2005.
Kerr D. Capecitabine/irinotecan in colorectal cancer: European early-phase data and planned trials. Oncology 2002; 16(suppl):12-5.
Thomas Cartwright et al, Results of a Phase II Trial of Cetuximab plus Capecitabine/Irinotecan as First-Line Therapy for Patients with Advanced and/or Metastatic Colorectal Cancer
Journal Clinical Colorectal Cancer Volume 7, Number 6 / November 2008 Pages 390-397