title: Induction chemotherapy followed by concomitant chemoradiotherapy for advanced head and neck cancer: impact on the natural history of the disease.
abstract: OBJECTIVE
  To determine survival rates and the pattern of failure in head and neck cancer patients treated with induction chemotherapy, limited surgery and concomitant chemoradiotherapy.
  
  
  METHODS
  Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy. Surgical resection was performed with the intent to spare organ function.
  
  
  RESULTS
  Seventy-one patients were treated at three institutions. Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achieved a clinical complete response (CR) to PFL-IFN. Local therapy consisted of surgery in 37 and/or FHX in 55 patients. With a median follow-up duration of 37 months, there have been 20 recurrences (15 local, four distant, and one both local and distant), and 29 deaths, 15 in patients with disease progression and 14 not directly related to the primary tumor. Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60% (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mucositis (54%) and myelosuppression (60%). Five patients died of toxicity. During FHX, 70% of patients had grade 3 or 4 mucositis.
  
  
  CONCLUSIONS
  PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant control and overall survival rates. Second malignancies and intercurrent medical disease emerge as major risks to long-term survival. In view of the high toxicity and long treatment duration, further modifications of this approach are required.
authors.affiliation: Department of Medicine, University of Chicago, IL, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: M
authors.initials: M
authors.lastname: Kies
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: W J
authors.initials: WJ
authors.lastname: Moran
authors.forename: M
authors.initials: M
authors.lastname: Kozloff
authors.forename: B
authors.initials: B
authors.lastname: Mittal
authors.forename: H
authors.initials: H
authors.lastname: Pelzer
authors.forename: B
authors.initials: B
authors.lastname: Wenig
authors.forename: W
authors.initials: W
authors.lastname: Panje
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D006918:Hydroxyurea