title: Randomized controlled trial to evaluate the effects of ethyl-2-cyanoacrylate on pain intensity and quality of life in head and neck cancer patients suffering from cetuximab-induced rhagades during radioimmunotherapy: the support trial.
abstract: BACKGROUND
  Cetuximab is a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR). Skin reactions are the most common side effects of cetuximab. Rhagades of the tips of the fingers and toes, the heels and especially the interphalangeal joints are one of the most frightening and painful dermatological side effects that may develop from EGFR-inhibitor therapy. Rhagades are characterized by pain, severe tenderness and poor healing response. They are challenging to treat. Thus, rhagades often poses the most significant threat to the quality of life (QoL) for these patients. Ethyl-2-cyanoacrylate (ECA), an ethyl ester of the 2-cyano-2-propenoic acid, is often used as adhesive in a variety of different work settings in industry, i.e. as a component in nail-care products such as nail glue. In addition, ECA is used for various medical indications, such as for liquid bandages and for suture-less surgery. Wound healing can be accelerated with ECA. The purpose of the SUPPORT trial is to investigate the efficacy of ECA for the treatment of cetuximab-induced rhagades and to assess the clinical usefulness of the SUPO score, a new classification system for rhagades induced by EGFR-inhibitor therapy.
  
  
  METHODS
  The SUPPORT trial is an open-label, prospective, randomized, national multicenter intervention study to evaluate the effectiveness of ECA versus the standard treatment of each institution on the pain intensity and QoL in patients with locally advanced head and neck cancer suffering from painful cetuximab-induced rhagades during radioimmunotherapy. Primary endpoint is the assessment of the pain intensity 24 hours after application of ECA or the standard treatment quantified by the visual analogue scale (VAS). Secondary endpoints are the evaluation of QoL assessed by the EORTC-QoL-C30 questionnaire and the Dermatological Life Quality Index (DLQI).
  
  
  CONCLUSIONS
  During treatment with EGFR inhibitors it is necessary to recognize and manage side effects promptly to assure better patient QoL. The SUPPORT trial is the first randomized clinical trial evaluating a new treatment option for painful cetuximab-induced rhagades. Furthermore, the new SUPO score will be prospectively assessed in terms of clinical usefulness for classification of EGFR inhibitor-induced rhagades.
  
  
  BACKGROUND
  Current Controlled Trials NCT01693159.
authors.affiliation: Department of Radiation Oncology, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. karin.potthoff@med.uni-heidelberg.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Potthoff
authors.forename: Gregor
authors.initials: G
authors.lastname: Habl
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.forename: Christian
authors.initials: C
authors.lastname: Suppan
authors.forename: Jessica
authors.initials: J
authors.lastname: Hassel
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Martin
authors.initials: M
authors.lastname: Indorf
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000068818:Cetuximab; D003487:Cyanoacrylates / Q000008:administration & dosage*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D016499:Radioimmunotherapy / Q000009:adverse effects; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003487:Cyanoacrylates; C029054:ethyl 2-cyanoacrylate; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
references.citation: Expert Opin Ther Targets. 2012 Jan;16(1):15-31
references.pmid: 22239438
references.citation: Int J Dermatol. 2011 Feb;50(2):129-46
references.pmid: 21244375
references.citation: Ann Oncol. 2005 Sep;16(9):1425-33
references.pmid: 16012181
references.citation: Rev Med Interne. 2012 May;33(5):273-8
references.pmid: 22385684
references.citation: Dtsch Med Wochenschr. 2010 Jan;135(4):149-54
references.pmid: 20101558
references.citation: Lancet Oncol. 2010 Jan;11(1):21-8
references.pmid: 19897418
references.citation: Eur J Dermatol. 2010 Jan-Feb;20(1):82-4
references.pmid: 19797039
references.citation: J Am Acad Dermatol. 2007 Feb;56(2):317-26
references.pmid: 17141360
references.citation: Support Care Cancer. 2011 Aug;19(8):1079-95
references.pmid: 21630130
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: BMC Cancer. 2013 Jul 15;13:345
references.pmid: 23855804
references.citation: J Natl Compr Canc Netw. 2009 May;7 Suppl 1:S5-21; quiz S22-4
references.pmid: 19470276
references.citation: Oncogene. 2000 Dec 27;19(56):6550-65
references.pmid: 11426640
references.citation: Otolaryngol Head Neck Surg. 2004 Mar;130(3):351-6
references.pmid: 15054378
references.citation: J Dtsch Dermatol Ges. 2011 Mar;9(3):195-203
references.pmid: 21059173
references.citation: Cancer. 2008 Aug 15;113(4):847-53
references.pmid: 18543329
references.citation: J Dtsch Dermatol Ges. 2005 Aug;3(8):599-606
references.pmid: 16033478
references.citation: J Clin Oncol. 2005 Jan 1;23(1):165-74
references.pmid: 15557594
references.citation: Ann Oncol. 2011 Mar;22(3):524-535
references.pmid: 20709812
references.citation: Target Oncol. 2009 Apr;4(2):107-19
references.pmid: 19452131
references.citation: Curr Oncol. 2009 Jan;16(1):16-26
references.pmid: 19229368
references.citation: Clin Colorectal Cancer. 2005 Apr;5 Suppl 1:S19-27
references.pmid: 15871762
references.citation: Eur J Cancer. 2007 Jan;43(1):35-45
references.pmid: 17098420
references.citation: Exp Cell Res. 2011 Nov 15;317(19):2765-71
references.pmid: 21925171
references.citation: Front Biosci (Schol Ed). 2011 Jan 01;3:454-66
references.pmid: 21196389
references.citation: N Engl J Med. 2006 Feb 9;354(6):567-78
references.pmid: 16467544