Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck.
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.
Rodríguez
Marta Osorio
MO
National Institute of Oncology and Radiobiology, Havana, Cuba.
Rivero
Teresa Cruz
TC
del Castillo Bahi
Ramón
R
Muchuli
Carlos Roca
CR
Bilbao
Miguel Azcue
MA
Vinageras
Elia Neninger
EN
Alert
José
J
Galainena
Julio Jiménez
JJ
Rodríguez
Edmundo
E
Gracias
Elías
E
Mulén
Bárbara
B
Wilkinson
Bárbara
B
de Armas
Esther Lucía
EL
Pérez
Kirenia
K
Pineda
Idael
I
Frómeta
Milagros
M
Leonard
Idrissa
I
Mullens
Vladimir
V
Viada
Carmen
C
Luaces
Patricia
P
Torres
Olga
O
Iznaga
Normando
N
Crombet
Tania
T
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C501466:nimotuzumab; D000068818:Cetuximab