Xeliri second line for metastatic colorectal cancer – pro

The issue that we will discuss is Xeliri (Xeloda and irinotecan) in second or later line of therapy. It is a tempting regimen because Xeldoa is an generally effective drug for colorectal cancer and it is oral.  We start by pointing out that there are now six different classes of drugs with significant antitumor activity in colon cancer:

Fluoropyrimidine (5-fluorouracil [5-FU] which is usually given with leucovorin [LV], capecitabine, tegafur plus uracil [UFT]). Irinotecan, Oxaliplatin, Cetuximab and panitumumab. The latter two are monoclonal antibodies (MoAbs) directed against the epidermal growth factor receptor (EGFR), and bevacizumab, is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Zaltrap was recenlty(2012) also approved.

The best way to combine and sequence all of these drugs to optimize treatment is not yet established, although for intial treatment of metasatic colorectal cancer NCCN recommends combinations of 5FU and Lekovorin with oxaliplatin or irinotecan with or without Avastin, CAPEOX, 5FU/Leukovorin, Xeloda and Avastin or Folfoxiri.

For second or third line therapy, single agents are acceptable and NCCN lists irinotecan as a single agent. It also lists combinations, see p. COL-C of the NCCN guideline for colon cancer. NCCN has a complex schema when to give what for second line and also lists irinnotecan or Folfiri with Erbitux, Zaltrap or Vectbix. However, it does not list irinotecan with Xeloda.

NCCN, Colon cancer 2012

Van Cutsem E, Köhne CH, Láng I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011; 29:2011.

Ogino S, Shima K, Meyerhardt JA, et al. Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803. Clin Cancer Res 2012; 18:890.

Bokemeyer C, Cutsem EV, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 2012.

Braun MS, Richman SD, Quirke P, et al. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol 2008; 26:2690.

Boige V, Mendiboure J, Pignon JP, et al. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. J Clin Oncol 2010; 28:2556.

Goldberg RM, Rothenberg ML, Van Cutsem E, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 2007; 12:38.

Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst 2011; 103:21.

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