Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

Borner, Markus; Koeberle, Dieter; Moos, Roger von; Saletti, Piercarlo; Rauch, Daniel; Hess, Viviane; Trojan, Andreas; Helbling, Daniel; Paulweber, Bernhard; Caspar, Clemens B.; Ruhstaller, Thomas; Roth, Arnaud; Каппелер, Андреас; Dietrich, Damien; Lanz, Doris; Mingrone, Walter

doi:10.1093/annonc/mdn058

Cited by 116 publications

(98 citation statements)

References 22 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prelimary data from two small randomized phase II studies (Borner et al, 2006;Heinemann et al, 2006) were also presented. One study showed that addition of Cx to XELOX increased RR (from 27 to 43%) and another study showed that the combination of XELOX and Cx increased RR from 42 to 66% compared with XELIRI and Cx.…”

Section: First-line Therapymentioning

confidence: 99%

Current role of antibody therapy in patients with metastatic colorectal cancer

2007

View full text Add to dashboard Cite

Section: First-line Therapymentioning

confidence: 99%

Current role of antibody therapy in patients with metastatic colorectal cancer

2007

View full text Add to dashboard Cite

“…All these studies indicated that only a subgroup of patients treated with cetuximab may benefit from the drug (Rosenberg et al, 2002;Van Laethem et al, 2003;Cunningham et al, 2004;Saltz et al, 2001Saltz et al, , 2004Tabernero et al, 2004;Jennis et al, 2005;Borner et al, 2006;Folprecht et al, 2006;Venook et al, 2006;Wilke et al, 2006). Based on preclinical findings, it should be outlined that the trials including cetuximab have been performed in patients who expressed EGFR protein in primary tumours based on immunohistochemistry (IHC).…”

mentioning

confidence: 99%

PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

et al. 2007

View full text Add to dashboard Cite

To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy ( P <0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR ( P <0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity ( P <0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.

show abstract

“…After the initial pivotal randomised phase II BOND study which demonstrated the ability of cetuximab to circumvent chemotherapy resistance , a series of randomised phase II -III trials for EGFR-targeted monoclonal antibodies (mAbs) have been reported. Table 2 shows the results of these trials Jonker et al, 2007;Tejpar et al, 2007;Van Cutsem et al, 2007Borner et al, 2008;Ciuleanu et al, 2008;Heinemann et al, 2008;Sobrero et al, 2008;Wilke et al, 2008;Bokemeyer et al, 2009;Hecht et al, 2009). All these studies supported the biological activity of cetuximab in advanced CRC.…”

Section: Epidermal Growth Factor Receptormentioning

confidence: 78%

Treatment in advanced colorectal cancer: what, when and how?

Chau

Cunningham

2009

Br J Cancer

View full text Add to dashboard Cite

Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC.

show abstract

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

Abstract: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.

Cited by 116 publications

References 22 publications

Current role of antibody therapy in patients with metastatic colorectal cancer

Current role of antibody therapy in patients with metastatic colorectal cancer

PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

Treatment in advanced colorectal cancer: what, when and how?

Contact Info

Product

Resources

About