title: Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC.
  
  
  METHODS
  In this Phase I/II trial 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment.
  
  
  RESULTS
  The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively.
  
  
  CONCLUSIONS
  This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. herchenhorn@hotmail.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Herchenhorn
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Dias
authors.forename: Célia M P
authors.initials: CM
authors.lastname: Viegas
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Federico
authors.forename: Carlos Manoel M
authors.initials: CM
authors.lastname: Araújo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Small
authors.forename: Marcos
authors.initials: M
authors.lastname: Bezerra
authors.forename: Karina
authors.initials: K
authors.lastname: Fontão
authors.forename: Renata E
authors.initials: RE
authors.lastname: Knust
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Ferreira
authors.forename: Renato G
authors.initials: RG
authors.lastname: Martins
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001938:Brazil; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D000069347:Erlotinib Hydrochloride; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D011879:Radiotherapy Dosage; D016879:Salvage Therapy / Q000379:methods; D015996:Survival Rate
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin