title: Gemcitabine and cisplatin in a concomitant alternating chemoradiotherapy program for locally advanced head-and-neck cancer: a pharmacology-guided schedule.
abstract: OBJECTIVE
  Administration of gemcitabine together with cisplatin at cytotoxic doses in a chemoradiotherapy regimen is hampered by a high degree of local toxicity. Using the pharmacologic properties of the drug we designed a modified schedule aimed at reducing toxicity while preserving activity.
  
  
  METHODS
  Patients with squamous cell carcinomas of the oral cavity, pharynx and larynx, bulky T4, and/or N2 to N3 were eligible. Gemcitabine was administered at a dose of 800 mg/m2 on Days 1 and 12 and cisplatin at a dose of 20 mg/m2 on Days 2 to 5, every 21 days for 3 courses. Radiotherapy, delivered with standard fractionation, was given on Days 8 to 12 and 15 to 19 and was repeated 3 times up to a total dose of > or = 60 Gy.
  
  
  RESULTS
  A total of 28 patients were selected. Grade 3 to 4 stomatitis was recorded in 25 patients (89%). Thirteen patients (46%) experienced Grade 3 to 4 neutropenia. Febrile neutropenia occurred in 8 patients (29%) and in 2 was complicated by infection and death. The overall complete response rate was 79%. At a median follow up of 71 months, 11 patients had a locoregional relapse (3-year locoregional control, 64%); 6 patients had distant metastases, among whom only 2 were without locoregional recurrence. The 3-year progression-free survival is 39% and 3-year overall survival has been 43%.
  
  
  CONCLUSIONS
  The schedule modification did not attenuate local toxicity. Moreover, infections and especially pneumonia, were a major problem. The high activity of gemcitabine when combined with radiotherapy would most likely be better exploited in the context of modified radiation schemes.
authors.affiliation: Medical Oncology, S. Croce General Hospital, Cuneo, Italy. gianmauro.numico@fastwebnet.it
authors.forename: Gianmauro
authors.initials: G
authors.lastname: Numico
authors.forename: Elvio G
authors.initials: EG
authors.lastname: Russi
authors.forename: Raffele
authors.initials: R
authors.lastname: Vitiello
authors.forename: Raffaele
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Ida
authors.initials: I
authors.lastname: Colantonio
authors.forename: Marco
authors.initials: M
authors.lastname: Cipolat
authors.forename: Riccardo Vigna
authors.initials: RV
authors.lastname: Taglianti
authors.forename: Antonio
authors.initials: A
authors.lastname: Pelissero
authors.forename: Elena
authors.initials: E
authors.lastname: Fea
authors.forename: Cristina
authors.initials: C
authors.lastname: Granetto
authors.forename: Gianna
authors.initials: G
authors.lastname: Di Costanzo
authors.forename: Milena
authors.initials: M
authors.lastname: Gasco
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
authors.forename: Marcella
authors.initials: M
authors.lastname: Occelli
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009503:Neutropenia / Q000209:etiology; D010610:Pharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D013280:Stomatitis / Q000209:etiology / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine