title: Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.
abstract: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose.
  
  
  
  Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned.
  
  
  
  Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease.
  
  
  
  Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.
authors.affiliation: Departments of Radiation Oncology.|Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Ahn
authors.affiliation: Departments of Radiation Oncology.|Department of Radiation Oncology, Case Western Reserve University, Cleveland.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Pramila R
authors.initials: PR
authors.lastname: Anne
authors.affiliation: Otolaryngology.
authors.forename: David
authors.initials: D
authors.lastname: Cognetti
authors.affiliation: Otolaryngology.
authors.forename: William M
authors.initials: WM
authors.lastname: Keane
authors.affiliation: Departments of Radiation Oncology.|Department of Radiation Oncology, Ohio State University, Columbus, OH.
authors.forename: Evan
authors.initials: E
authors.lastname: Wuthrick
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Medical Oncology, Sidney Kimmel Medical College of Thomas, Jefferson University.
authors.forename: Rita S
authors.initials: RS
authors.lastname: Axelrod
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel / Q000008:administration & dosage; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000077143:Docetaxel; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin; D005472:Fluorouracil