The small EVEREST trial has shown that the concept of guiding cetuximab dose escalation using the clinical parameter of acneiform skin rash is safe. However, as no significant increase of cetuximab efficacy could be observed, data from the ongoing EVEREST II trial must be awaited before dose escalation can be considered for clinical use.
Key Points
Higher doses of cetuximab are well tolerated and lead to increased grade ≥2 acneiform rashes; we await the results from the prospective EVEREST II trial, which will test whether patients with increased acneiform rash have longer overall survival
This is a preview of subscription content, log in via an institution to check access.
References
Van Cutsem, E. et al. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J. Clin. Oncol. http://dx.doi.org/10.1200/JCO.2011.40.9243
Cunningham, D. et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351, 337–345 (2004).
Moore, M. J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 25, 1960–1966 (2007).
Douillard, J. et al. Randomized, open-label, phase III study of panitumumab (pmab) with FOLFOX4 versus FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): efficacy by skin toxicity (ST) [abstract 3528^). J. Clin. Oncol. 28 (Suppl.), 15s (2010).
Lenz, H. J. et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J. Clin. Oncol. 24, 4914–4921 (2006).
Fracasso, P. M. et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin. Cancer Res. 13, 986–993 (2007).
Shin, D. M. et al. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin. Cancer Res. 7, 1204–1213 (2001).
Mascia, F. et al. EGFR regulates the expression of keratinocyte-derived granulocyte/macrophage colony-stimulating factor in vitro and in vivo. J. Invest. Dermatol. 130, 682–693 (2010).
Tabernero, J. et al. Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose-escalation study. J. Clin. Oncol. 28, 1181–1189 (2010).
Diaz, L. A. Jr et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486, 537–540 (2012).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
S. Stintzing has received honoraria (speakers bureau) from the following companies: Amgen, Merck KGaA and Roche. H.-J. Lenz has received honoraria (speakers bureau) from and acted as a consultant for Merck KGaA.
Rights and permissions
About this article
Cite this article
Stintzing, S., Lenz, HJ. Cetuximab dosing by rash—is the scaling of EVEREST meaningful?. Nat Rev Clin Oncol 9, 554–556 (2012). https://doi.org/10.1038/nrclinonc.2012.142
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrclinonc.2012.142
- Springer Nature Limited