title: Accelerated hyperfractionated radiotherapy and concurrent protracted venous infusion chemotherapy in locally advanced head and neck cancer.
abstract: Concurrent radiotherapy and chemotherapy result in a significant benefit with respect to induction chemotherapy followed by radiotherapy or radiotherapy alone, although with a significant increase of toxicity. To discover a more tolerated and effective chemoradiation regimen, the feasibility and efficacy of a hyperfractionated accelerated irradiation with concurrent protracted venous infusion chemotherapy was investigated. Sixty-five patients with advanced head and neck cancer underwent a definitive (53 patients) or a postoperative adjuvant (12 patients) chemoradiation treatment. Chemotherapy consisted of an intravenous protracted infusion of 5 and 200 mg/m /d cisplatin and 5-fluorouracil, respectively. Radiotherapy consisted of a split-course accelerated hyperfractionation of two 150-cGy (split twice a day) or three 100-cGy fractions per day (split three times a day) at more than 6-hour intervals, for 2 weeks followed, after a 1-week interruption, by 2-to-3-week treatment, with the same fractionation schedule, to a total dose of 60 Gy to 69 Gy. Confluent mucositis was tolerable and was the cause of treatment delay of more than 10 days in only 20% of patients. Grade 3 or greater systemic toxicity occurred only in 9 of 65 (14%) patients and was never the cause of drug dose reduction. Complete responses were observed in 69% of patients with gross diseases. At a median follow-up of 43.5 months, 45% of patients were alive and free of disease and 38% died of cancer. The 5-year actuarial local regional failure was 35%. The 5-year actuarial disease-specific survival was 50%. Preservation of larynx function was achieved in 47% of living patients and in 74% of all patients, with advanced tumors of the laryngopharynx. The long-term results of this study suggest that this chemoradiation regimen has the potential of achieving a significant improvement over standard therapy while avoiding significant toxicity.
authors.affiliation: Regina Elena National Cancer Institute, Division of Radiation Oncology, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arcangeli
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Saracino
authors.forename: Donatella Tirindelli
authors.initials: DT
authors.lastname: Danesi
authors.forename: Enrico
authors.initials: E
authors.lastname: De Campora
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giovinazzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.forename: Stefano
authors.initials: S
authors.lastname: Arcangeli
authors.forename: Antonella
authors.initials: A
authors.lastname: Mecozzi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010610:Pharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010865:Pilot Projects; D016019:Survival Analysis
chemical_list: D002945:Cisplatin; D005472:Fluorouracil