title: Could the Addition of Cetuximab to Conventional Radiation Therapy Improve Organ Preservation in Those Patients With Locally Advanced Larynx Cancer Who Respond to Induction Chemotherapy? An Organ Preservation Spanish Head and Neck Cancer Cooperative Group Phase 2 Study.
abstract: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors.
  
  
  
  This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy.
  
  
  
  A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT.
  
  
  
  According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted.
authors.affiliation: Medical Oncology Department, Universitat de Barcelona, IDIBELL, Institut Català d'Oncologia-L'Hospitalet, Barcelona, Spain. Electronic address: rmesia@iconcologia.net.
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesía
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garcia-Saenz
authors.affiliation: Radiation Oncology Department, IDIBELL, Institut Català d'Oncologia-L'Hospitalet, Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lozano
authors.affiliation: Medical Oncology Department, Hospital Universitario La Fe, València, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pastor
authors.affiliation: Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Grau
authors.affiliation: Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Trufero
authors.affiliation: Medical Oncology Department, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Lambeaz
authors.affiliation: Medical Oncology Department, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Martínez-Galán
authors.affiliation: Medical Oncology Department, Hospital Xeral de Lugo, Lugo, Spain.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Mel
authors.affiliation: Medical Oncology Department, Hospital Son Llatzer, Palma de Mallorca, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: González
authors.affiliation: Medical Oncology Department, Universitat de Barcelona, IDIBELL, Institut Català d'Oncologia-L'Hospitalet, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vázquez
authors.affiliation: Department of Otorhinolaryngology, Hospital Universitari de Bellvitge-University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Mañós
authors.affiliation: Medical Oncology Department, Universitat de Barcelona, IDIBELL, Institut Català d'Oncologia-L'Hospitalet, Barcelona, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Taberna
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia, Badalona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cirauqui
authors.affiliation: Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Del Barco
authors.affiliation: Medical Oncology Department, Hospital General de Manresa, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Casado
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia, Girona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rubió-Casadevall
authors.affiliation: Medical Oncology Department, Hospital San Pedro de Alcántara, Cáceres, Spain.
authors.forename: Angles
authors.initials: A
authors.lastname: Rodríguez-Jaráiz
authors.affiliation: Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Cruz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods*; D007822:Laryngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D007825:Laryngectomy; D007830:Larynx; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D059351:Organ Sparing Treatments / Q000009:adverse effects / Q000379:methods*; D011446:Prospective Studies; D013030:Spain; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil