title: Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy for Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial.
abstract: OBJECTIVE
  No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy.
  
  
  METHODS
  Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival.
  
  
  RESULTS
  The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms.
  
  
  CONCLUSIONS
  CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Stefano Maria
authors.initials: SM
authors.lastname: Magrini
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy. michela.buglione@unibs.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Buglione
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvò
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paiar
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ponticelli
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Petrucci
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Almalina
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Crociani
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Lastrucci
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Vecchio
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonomo
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Pasinetti
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Triggiani
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavagnini
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Costa
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Tonoli
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Maddalo
authors.affiliation: Stefano Maria Magrini, Michela Buglione, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, and Marta Maddalo, Brescia University, Istituto del Radio O. Alberti, Spedali Civili Hospital; Renzo Corvò, Almalina Bacigalupo, and Stefania Vecchio, Istituto Di Ricovero e Cura a Carattere Scientifico S. Martino, National Cancer Research Institute and University, Genova; Luigi Pirtoli and Monica Crociani, University of Siena, Siena; Fabiola Paiar and Pierluigi Bonomo, Azienda Ospedaliero-Universitaria Careggi, Firenze; Pietro Ponticelli and Luciana Lastrucci, S. Donato Hospital, Azienda Unità Sanitaria Locale No. 8, Arezzo; and Alessia Petrucci, Pistoia Hospital, Azienda Unità Sanitaria Locale No. 3, Pistoia; Salvatore Grisanti, Brescia University, Brescia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000068818:Cetuximab; D002945:Cisplatin