Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer

J Natl Cancer Inst. 1992 Jun 3;84(11):877-82. doi: 10.1093/jnci/84.11.877.


Background: The majority of patients with head and neck cancer die of locoregional recurrence of disease following surgery and/or radiotherapy.

Purpose: Our purpose was to administer induction chemotherapy, perform surgery, and administer concomitant chemoradiotherapy in rapid sequence and to evaluate their impact on locoregional and distant tumor control.

Methods: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was given to patients who were unable to receive bleomycin. Local therapy consisted of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea, leucovorin, and radiotherapy (FHX-L), all administered every other week.

Results: Complete and overall induction response rates were 21% and 79%, respectively, for PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81% of the patients were disease-free. With a median follow-up of 35 months, the median survival and time to progression are 22 and 17 months, respectively, for PBM and have not been reached for PFL. Locoregional recurrence of disease is 30% for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3% for PFL.

Conclusions: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL. The high distant failure (i.e., outside the head and neck area) rate of PBM suggests insufficient systemic activity for that regimen.

Implications: Concomitant FHX-L chemoradiotherapy may improve regional control rates of advanced head and neck cancer. Effective systemic therapy may be needed to control systemic micrometastases. PFL, but not PBM, appears to be suitable to accomplish that goal.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Carcinoma / diagnostic imaging
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cisplatin / administration & dosage
  • Combined Modality Therapy / adverse effects
  • Female
  • Fluorouracil / administration & dosage
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / surgery
  • Humans
  • Hydroxyurea / administration & dosage
  • Leucovorin / administration & dosage
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Radiography
  • Time Factors
  • Treatment Outcome


  • Bleomycin
  • Cisplatin
  • Leucovorin
  • Fluorouracil
  • Hydroxyurea
  • Methotrexate