title: Neoadjuvant docetaxel, cisplatin, 5-fluorouracil before concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck versus concomitant chemoradiotherapy: a phase II feasibility study.
abstract: OBJECTIVE
  To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared with the same CHT-RT regimen alone in locally advanced head-and-neck squamous cell carcinoma.
  
  
  METHODS
  We treated 24 patients (20 men and 4 women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years (range, 41-73 years). The stage distribution was as follows: Stage II, 1 patient; Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of 0 and 6 had a performance status of 1. None had undergone previous CHT or RT. Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on Days 1-4 and 5-fluorouracil 600 mg/m(2)/d continuous infusion for 96 h) starting on Days 1, 22, and 43 during RT (one daily fraction, 66-70 Gy within 33-35 fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75 mg/m(2), cisplatin 80 mg/m(2), 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) followed by the same CHT-RT regimen.
  
  
  RESULTS
  After the first 16 patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was modified. The limiting toxicity observed during concomitant CHT-RT was similar in Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4 mucositis and other relevant toxicity that did not allowing completion of CHT-RT without interruption occurred in 44% of the patients. A reduction of at least one cycle of concurrent CHT was required in 31% of patients. On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World Health Organization G3-G4 mucositis. No World Health Organization hematologic G3-G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1 patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and 3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1) and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3).
  
  
  CONCLUSIONS
  Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are feasible without limiting toxicity. Three cycles of TPF were well tolerated and did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase III study has been started with the aim of comparing two cycles of PF during RT as standard treatment vs. the experimental arm with three cycles of neoadjuvant TPF followed by two cycles of PF during RT.
authors.affiliation: Department of Medical Oncology, Ospedale Civile Venezia, Venice, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ghi
authors.forename: Adriano
authors.initials: A
authors.lastname: Paccagnella
authors.forename: Paola
authors.initials: P
authors.lastname: D'Amanzo
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Mione
authors.forename: Stefano
authors.initials: S
authors.lastname: Fasan
authors.forename: Stefano
authors.initials: S
authors.lastname: Paro
authors.forename: Cataldo
authors.initials: C
authors.lastname: Mastromauro
authors.forename: Rosa
authors.initials: R
authors.lastname: Carnuccio
authors.forename: Giacomo
authors.initials: G
authors.lastname: Turcato
authors.forename: Carlo
authors.initials: C
authors.lastname: Gatti
authors.forename: Adriano
authors.initials: A
authors.lastname: Pallini
authors.forename: Ottorino
authors.initials: O
authors.lastname: Nascimben
authors.forename: Rita
authors.initials: R
authors.lastname: Biason
authors.forename: Francesco
authors.initials: F
authors.lastname: Oniga
authors.forename: Michele
authors.initials: M
authors.lastname: Medici
authors.forename: Fabio
authors.initials: F
authors.lastname: Rossi
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Fila
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011879:Radiotherapy Dosage; D013280:Stomatitis / Q000209:etiology; D043823:Taxoids / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000209:etiology
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil