Radiation Therapy, Combination Chemotherapy, and Amifostine in Treating Patients With Head and Neck Cancer
Condition: Carcinoma of Unknown Primary; Head and Neck Cancer
MeSH terms: Carcinoma; Head and Neck Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
      chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
      die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side
      effects of radiation therapy and chemotherapy.

      PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination
      chemotherapy and amifostine in treating patients who have stage II, stage III, or stage IV
      head and neck cancer that cannot be surgically removed.
    

Detailed description: 
      OBJECTIVES: I. Assess the impact of amifostine on the acute tolerance of combined
      hyperfractionated radiation therapy and fluorouracil, cisplatin, and paclitaxel with
      amifostine, in terms of the grade and duration of acute mucositis and dermatitis, and acute
      hematologic tolerance in patients with stage III or IV unresectable head and neck carcinoma.
      II. Determine the local control and survival associated with this regimen in these patients.
      III. Determine the long term chronic toxic effects of this regimen in terms of swallowing
      dysfunction, PEG dependency, and xerostomia in these patients. IV. Determine the quality of
      life post therapy by assessment of speech and swallowing function in these patients. V.
      Determine if radiation dose escalation in patients with treatment interruption achieve an
      isoeffect on locoregional control. VI. Determine the safe optimal dose of paclitaxel to be
      combined with hyperfractionated radiation therapy, fluorouracil, cisplatin, and amifostine in
      these patients. VII. Determine the correlation of p53 chromosome expression on locoregional
      control and survival of these patients. VIII. Quantitate tumor volumetrics and correlate with
      stage, resectability status, and locoregional control and survival of these patients.

      OUTLINE: This is a dose escalation of paclitaxel, multicenter study. Patients are stratified
      by performance status, stage, institution, tumor volumetrics, resectability, and p53
      expression. Patients receive amifostine IV over 10 minutes on Monday of weeks 1, 5, and 9,
      and over 5-7 minutes Tuesday through Friday of weeks 1, 5, and 9 and Monday through Friday of
      weeks 2, 3, 4, 6, and 7. Within 10-15 minutes of amifostine administration, patients receive
      paclitaxel IV over 3 hours, cisplatin IV over 2 hours on days 1, 29, and 56, and fluorouracil
      IV over 72 hours on days 1-4, 29-33, and 56-60. Starting on day 2, patients receive
      hyperfractionated external beam radiotherapy twice daily over 6.5 weeks, following amifostine
      IV over 5-7 minutes Monday through Friday. Cohorts of 6-20 patients each receive escalating
      doses of paclitaxel. Quality of life is assessed. Patients are followed monthly for 1 year,
      every 2 months for 1 year, every 6 months for 3 years, and then annually thereafter until
      death.

      PROJECTED ACCRUAL: A minimum of 36 patients will be accrued for this study within 20 months.
    

Intervention name(s): amifostine trihydrate; cisplatin; fluorouracil; paclitaxel; quality-of-life assessment; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Paclitaxel; Fluorouracil; Amifostine
Primary purpose: Treatment
Keywords: squamous cell carcinoma of unknown primary; stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity