title: Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma. Feasibility and tolerability in elderly and chemotherapy-ineligible patients.
abstract: BACKGROUND
  Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. We analyzed a group of patients treated at our institute with cetuximab plus volumetric modulation arc therapy (VMAT) with the RapidArc technique in a simultaneous integrated boost (SIB) regime. The primary end point was the assessment of acute toxicity and the feasibility of the combined approach.
  
  
  METHODS
  Between December 2008 and March 2010, 22 patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities (the majority suffered of heart chronic diseases). All patients underwent planning CT (additional image modalities were acquired for contouring purposes in the same treatment position: MRI in 12 and FDG-PET in 4 out of 22 patients). VMAT, by means of RapidArc, and SIB with two dose levels of 54.45 Gy and 69.96 Gy in 33 fractions were adopted. All patients included in the analysis were concomitantly treated with cetuximab: administration of the drug was initiated 1 week before RT at a loading dose of 400 mg/m(2) body surface area over a period of 120 min, follow by a weekly 60 min infusion of 250 mg/m(2) for the duration of RT. Patients were assessed for toxicities according to the Radiation Therapy Oncology Group (RTOG) criteria.
  
  
  RESULTS
  All but 2 patients completed treatment and achieved the minimum follow-up of 12 months after the end of the treatment. Of the 22 patients, 18% (4 patients) showed grade 1, 36% (8 patients) grade 2, and 36% (8 patients) showed grade 3 dermatitis, while 9% (2 patients) had grade 1, 36% (8 patients) grade 2, and 45% (10 patients) had grade 3 mucositis/stomatitis. No grade 4 toxicities were recorded. Considering blood parameters, 3 cases of grade 1 anemia and 1 case of grade 2 thrombocytopenia were observed. Nobody required feeding tube placement during treatment.
  
  
  CONCLUSIONS
  The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.
authors.affiliation: Radiotherapy and Radiosurgery, Humanitas Cancer Center, Istituto Clinico Humanitas, Via Manzoni 56, 20098, Rozzano (Milan), Italy. filippo.alongi@humanitas.it
authors.forename: F
authors.initials: F
authors.lastname: Alongi
authors.forename: M
authors.initials: M
authors.lastname: Bignardi
authors.forename: I
authors.initials: I
authors.lastname: Garassino
authors.forename: S
authors.initials: S
authors.lastname: Pentimalli
authors.forename: R
authors.initials: R
authors.lastname: Cavina
authors.forename: P
authors.initials: P
authors.lastname: Mancosu
authors.forename: G
authors.initials: G
authors.lastname: Reggiori
authors.forename: A
authors.initials: A
authors.lastname: Poletti
authors.forename: D
authors.initials: D
authors.lastname: Ferrari
authors.forename: P
authors.initials: P
authors.lastname: Foa
authors.forename: A
authors.initials: A
authors.lastname: Bigoni
authors.forename: A
authors.initials: A
authors.lastname: Dragonetti
authors.forename: P
authors.initials: P
authors.lastname: Salvatori
authors.forename: O
authors.initials: O
authors.lastname: Spahiu
authors.forename: A
authors.initials: A
authors.lastname: Fogliata
authors.forename: L
authors.initials: L
authors.lastname: Cozzi
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: M
authors.initials: M
authors.lastname: Scorsetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D058958:Organs at Risk; D010039:Otorhinolaryngologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011832:Radiation Injuries / Q000209:etiology; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab