title: Phase II study of induction chemotherapy with TPF followed by radioimmunotherapy with Cetuximab and intensity-modulated radiotherapy (IMRT) in combination with a carbon ion boost for locally advanced tumours of the oro-, hypopharynx and larynx--TPF-C-HIT.
abstract: BACKGROUND
  Long-term locoregional control in locally advanced squamous cell carcinoma of the head and neck (SCCHN) remains challenging. While recent years have seen various approaches to improve outcome by intensification of treatment schedules through introduction of novel induction and combination chemotherapy regimen and altered fractionation regimen, patient tolerance to higher treatment intensities is limited by accompanying side-effects. Combined radioimmunotherapy with cetuximab as well as modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) and carbon ion therapy (C12) are able to limit toxicity while maintaining treatment effects. In order to achieve maximum efficacy with yet acceptable toxicity, this sequential phase II trial combines induction chemotherapy with docetaxel, cisplatin, and 5-FU (TPF) followed by radioimmunotherapy with cetuximab as IMRT plus carbon ion boost. We expect this approach to result in increased cure rates with yet manageable accompanying toxicity.
  
  
  METHODS
  The TPF-C-HIT trial is a prospective, mono-centric, open-label, non-randomized phase II trial evaluating efficacy and toxicity of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 50 patients with histologically proven locally advanced SCCHN following TPF induction chemotherapy. Patients receive 24 GyE carbon ions (8 fractions) and 50 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy. Primary endpoint is locoregional control at 12 months, secondary endpoints are disease-free survival, progression-free survival, overall survival, acute and late radiation effects as well as any adverse events of the treatment as well as quality of life (QoL) analyses.
  
  
  CONCLUSIONS
  The primary objective of TPF-C-HIT is to evaluate efficacy and toxicity of cetuximab in combination with combined IMRT/carbon ion therapy following TPF induction in locally advanced SCCHN.
authors: Dept. of Radiation, Oncology INF, Heidelberg Germany. alexandra.jensen@med.uni-heidelberg.de
authors: Alexandra D
authors: AD
authors: Jensen
authors: Jürgen
authors: J
authors: Krauss
authors: Karin
authors: K
authors: Potthoff
authors: Almaz
authors: A
authors: Desta
authors: Gregor
authors: G
authors: Habl
authors: Athanasios
authors: A
authors: Mavtratzas
authors: Christine
authors: C
authors: Windemuth-Kiesselbach
authors: Jürgen
authors: J
authors: Debus
authors: Marc W
authors: MW
authors: Münter
references: Cancer Res. 1999 Apr 15;59(8):1935-40
references: 10213503
references: N Engl J Med. 2007 Oct 25;357(17):1695-704
references: 17960012
references: Cancer Res. 2002 Dec 15;62(24):7350-6
references: 12499279
references: BMC Cancer. 2006 Jan 31;6:28
references: 16448551
references: Lancet Oncol. 2010 Jan;11(1):21-8
references: 19897418
references: Radiother Oncol. 2001 Dec;61(3):275-80
references: 11730997
references: Arch Otolaryngol Head Neck Surg. 2008 May;134(5):536-8
references: 18490577
references: Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1301-11
references: 15275713
references: J Clin Oncol. 2005 Dec 1;23(34):8636-45
references: 16275937
references: J Clin Oncol. 2003 Jan 1;21(1):92-8
references: 12506176
references: Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16
references: 10924966
references: Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):449-57
references: 17363188
references: Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):171-7
references: 17056193
references: Cancer. 2005 Jul 15;104(2):338-44
references: 15937907
references: Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):175-84
references: 14697436
references: J Natl Cancer Inst. 1999 Dec 15;91(24):2081-6
references: 10601378
references: Int J Radiat Oncol Biol Phys. 2008 Jul 1;71(3):676-81
references: 18355979
references: Clin Cancer Res. 2000 Feb;6(2):701-8
references: 10690556
references: N Engl J Med. 2007 Oct 25;357(17):1705-15
references: 17960013
references: Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):S112-4
references: 17848275
references: J Clin Oncol. 1998 Apr;16(4):1310-7
references: 9552031
references: Lancet. 2006 Sep 2;368(9538):843-54
references: 16950362
references: Radiother Oncol. 2000 Aug;56(2):135-50
references: 10927132
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: Radiother Oncol. 2003 Dec;69(3):227-36
references: 14644481
references: Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):113-23
references: 14697428
references: Lancet. 2000 Mar 18;355(9208):949-55
references: 10768432
references: N Engl J Med. 2006 Feb 9;354(6):567-78
references: 16467544
references: Radiother Oncol. 2009 Jul;92(1):4-14
references: 19446902
references: Cancer Res. 1993 Oct 1;53(19):4637-42
references: 8402640
references: Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91
references: 17145528