Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study.
BACKGROUND
Intensification of chemoradiation for advanced head and neck squamous cell carcinoma (HNSCC) is unlikely due to toxicity. Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations. Therefore, cetuximab could intensify chemoradiation without worsening toxicity. We conducted a phase II study of chemoradiation and cetuximab.


METHODS
Eligible patients had stage III-IV M0 HNSCC. Treatment consisted of three cycles of cisplatin (20 mg/m(2)/day × 5 days) and fluorouracil (200 mg/m(2)/day × 5 days) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab. The primary end point of the study was complete response (CR) rate. Secondary end points were toxicity, progression-free survival (PFS) and overall survival (OS).


RESULTS
Fourty-five patients were enrolled: median age was 56 years, 38 had stage IV disease and 40 nodal involvement. CR occurred in 32 patients (71%). PFS and OS was 21+ months and 32.6+, respectively. Acute grade 3-4 toxic effects were in the expected range, but grade 3 radiodermatitis occurred in 33 patients.


CONCLUSIONS
The combination of cetuximab, cisplatin, fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy. The only unexpected toxicity was skin toxicity: grade 3 radiodermatitis occurred in 73% of the patients.
Merlano
M
M
Department of Medical Oncology. Electronic address: mcmerlano@tiscali.it.
Russi
E
E
Department of Radiation Therapy, S. Croce General Hospital, Cuneo.
Benasso
M
M
Department of Medical Oncology, La Spezia General Hospital, La Spezia.
Corvò
R
R
Department of Radiation Therapy, National Institute for Cancer Research, Genoa.
Colantonio
I
I
Department of Medical Oncology.
Vigna-Taglianti
R
R
Department of Radiation Therapy, S. Croce General Hospital, Cuneo.
Vigo
V
V
Department of Medical Oncology, La Spezia General Hospital, La Spezia.
Bacigalupo
A
A
Department of Radiation Therapy, National Institute for Cancer Research, Genoa.
Numico
G
G
Department of Medical Oncology, Aosta General Hospital, Aosta.
Crosetto
N
N
Department of Medical Oncology.
Gasco
M
M
Department of Medical Oncology.
Lo Nigro
C
C
Department of Medical Oncology.
Vitiello
R
R
Department of Otorhinolaryngology.
Violante
S
S
Clinical Trials Office, Department of Medical Oncology, S. Croce General Hospital, Cuneo, Italy.
Garrone
O
O
Department of Medical Oncology.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011855:Radiodermatitis / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002945:Cisplatin