title: Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck.
abstract: The prognosis of patients with advanced head and neck cancer remain dismal. For this tumor type, elevated levels of EGFR are associated with a shorter disease free survival and time to treatment failure, reflecting a more aggressive phenotype. Nimotuzumab is a humanized monoclonal antibody that recognizes domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by cetuximab and the binding site for EGF. In order to assess the efficacy of nimotuzumab in combination with radiotherapy, a controlled, double blind, randomized clinical trial was conducted in 106 advanced squamous cell carcinoma of the head and neck patients, mostly, unfit for chemoradiotherapy. Control patients received a placebo and radiotherapy. Treatment was safe and the most frequent adverse events consisted on grade I or II asthenia, fever, headache and chills. No skin rash was detected. A significant complete response rate improvement was found in the group of patients treated with nimotuzumab as compared to the placebo. In the intent to treat analysis, a trend towards survival benefit for nimotuzumab treated subjects was found. The survival benefit became significant when applying the Harrington-Fleming test, a weighted log-rank that underscores the detection of differences deferred on time. In addition, a preliminary biomarker investigation showed a significant survival improvement for nimotuzumab treated patients as compared to controls for subjects with EGFR positive tumors. All patients showed a quality of life improvement and a reduction of the general and specific symptoms of the disease.
authors.affiliation: National Institute of Oncology and Radiobiology, Havana, Cuba.
authors.forename: Marta Osorio
authors.initials: MO
authors.lastname: Rodríguez
authors.forename: Teresa Cruz
authors.initials: TC
authors.lastname: Rivero
authors.forename: Ramón
authors.initials: R
authors.lastname: del Castillo Bahi
authors.forename: Carlos Roca
authors.initials: CR
authors.lastname: Muchuli
authors.forename: Miguel Azcue
authors.initials: MA
authors.lastname: Bilbao
authors.forename: Elia Neninger
authors.initials: EN
authors.lastname: Vinageras
authors.forename: José
authors.initials: J
authors.lastname: Alert
authors.forename: Julio Jiménez
authors.initials: JJ
authors.lastname: Galainena
authors.forename: Edmundo
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Elías
authors.initials: E
authors.lastname: Gracias
authors.forename: Bárbara
authors.initials: B
authors.lastname: Mulén
authors.forename: Bárbara
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Esther Lucía
authors.initials: EL
authors.lastname: de Armas
authors.forename: Kirenia
authors.initials: K
authors.lastname: Pérez
authors.forename: Idael
authors.initials: I
authors.lastname: Pineda
authors.forename: Milagros
authors.initials: M
authors.lastname: Frómeta
authors.forename: Idrissa
authors.initials: I
authors.lastname: Leonard
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mullens
authors.forename: Carmen
authors.initials: C
authors.lastname: Viada
authors.forename: Patricia
authors.initials: P
authors.lastname: Luaces
authors.forename: Olga
authors.initials: O
authors.lastname: Torres
authors.forename: Normando
authors.initials: N
authors.lastname: Iznaga
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D016022:Case-Control Studies; D000068818:Cetuximab; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005076:Exanthema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000532:radiotherapy; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C501466:nimotuzumab; D000068818:Cetuximab