title: Weekly gemcitabine and cisplatin in combination with radiotherapy in patients with locally advanced head-and-neck cancer: Phase I study.
abstract: OBJECTIVE
  To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation.
  
  
  METHODS
  Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m(2) and that of gemcitabine was 10 mg/m(2) in 3 patients, with a subsequent dose escalation of 10 mg/m(2) of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m(2) for each new cohort was used (Level 1, 10 mg/m(2) of gemcitabine and 20 mg/m(2) of cisplatin; Level 2, 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin; and Level 3, 20 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy.
  
  
  RESULTS
  From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free.
  
  
  CONCLUSIONS
  Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin with an acceptable tolerability profile.
authors.affiliation: Radiation Oncology Department, Faculty of Medicine of Marilia, São Paulo, Brazil. gusviani@gmail.com
authors.forename: Gustavo Arruda
authors.initials: GA
authors.lastname: Viani
authors.forename: Sergio Luis
authors.initials: SL
authors.lastname: Afonso
authors.forename: Vivian Cardoso
authors.initials: VC
authors.lastname: Tavares
authors.forename: Lucas Godoi Bernardes
authors.initials: LG
authors.lastname: da Silva
authors.forename: Eduardo Jose
authors.initials: EJ
authors.lastname: Stefano
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011855:Radiodermatitis / Q000473:pathology; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012074:Remission Induction; D013280:Stomatitis / Q000209:etiology / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine