Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival

J Clin Oncol. 1998 Aug;16(8):2715-21. doi: 10.1200/JCO.1998.16.8.2715.


Purpose: To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented.

Patients and methods: Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy.

Results: Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis.

Conclusion: PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Hydroxyurea / administration & dosage
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Levoleucovorin
  • Male
  • Middle Aged
  • Radiotherapy Dosage
  • Recombinant Proteins
  • Remission Induction
  • Survival Rate


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Levoleucovorin
  • Cisplatin
  • Leucovorin
  • Fluorouracil
  • Hydroxyurea

Supplementary concepts

  • PFLI-alpha protocol