title: Phase II trial of vinorelbine, cisplatin and continuous infusion of 5-fluorouracil followed by hyperfractionated radiotherapy in locally advanced head and neck cancer.
abstract: OBJECTIVE
  We undertook a prospective phase II study to assess the feasibility and activity of a new induction chemotherapy regimen followed by hyperfractionated irradiation in locally advanced squamous cell head and neck cancer.
  
  
  METHODS
  25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m(2) i.v. day 1) and 5-fluorouracil (200 mg/m(2) continuous i.v. infusion day 1-21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily.
  
  
  RESULTS
  Chemotherapy was well tolerated, 6 patients developed grade 3 and one patient grade 4 neutropenia. Response to chemotherapy was observed in 19 patients (76%) including three complete responses and 16 partial responses. Planned bidRT was completed in 25 patients and all but one received planned bidRT dose without interruptions. Radiotherapy was well tolerated, mucositis was the most common side effect (grade 3-12 patients, grade 4-1 patient). At evaluation after the completion of bidRT, 13 patients had complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor progression. At the median follow-up of 18.2 months, 11 patients were alive and free of disease, and 14 patients had died (12 of tumor). Late xerostomy was observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1 patient.
  
  
  CONCLUSIONS
  bidRT preceded by ViFuP seems a feasible and active combination in locally advanced head and neck cancer. Good patient compliance did not compromise the delivery of planned dose of bidRT. However, short median duration of response (14.6 months) and moderate median overall survival (18.7 months) indicate the need for more intensive therapeutic strategies. On the basis of these results, modifications of our treatment schedule (shortening the overall treatment time by reduction of chemotherapy cycles and the use of chemotherapy concomitantly with irradiation) are planned for the future study.
authors.affiliation: Division of Radiotherapy, European Institute of Oncology, Milan, Italy. roberto.orecchia@ieo.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Jereczek-Fossa
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Catalano
authors.forename: Fausto
authors.initials: F
authors.lastname: Chiesa
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Pas
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masci
authors.forename: Marco
authors.initials: M
authors.lastname: Krengli
authors.forename: Andrea
authors.initials: A
authors.lastname: Vavassori
authors.forename: Fiora
authors.initials: F
authors.lastname: De Paoli
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marrocco
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.forename: Tommaso
authors.initials: T
authors.lastname: DePas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D015996:Survival Rate; D013997:Time Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D005472:Fluorouracil