Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Combination Chemotherapy in Treating Patients With Advanced or Locally Recurrent Cancer of the Head and Neck

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI DFCI-97130 NCI-G98-1385

Objectives

I. Define the maximum tolerated dose of docetaxel in patients with advanced or 
locally recurrent squamous cell carcinoma of the head and neck (SCCHN) or 
lymphoepithelioma.

II. Evaluate the toxic effects of docetaxel/cisplatin/fluorouracil/leucovorin 
calcium (TPFL) in this patient population.

III. Evaluate the feasibility of outpatient administration of fluorouracil and 
high dose leucovorin calcium.

IV. Determine the efficacy of TPFL in patients with advanced, previously 
untreated SCCHN or lymphoepithelioma.

Entry Criteria

Disease Characteristics:

Histologically proven advanced or locally recurrent squamous cell carcinoma 
of the head and neck (SCCHN) or lymphoepithelioma
  Previously untreated stage III or IV (M0) excluding patients with T3N0
   exophytic or T1N1 lesions
  No previous head and neck cancer, except patients treated solely with 
    surgery and recovered
  
Evaluable disease

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy for head and neck cancer

Endocrine therapy:
 Not specified

Radiotherapy:
 No prior radiotherapy for head and neck cancer

Surgery:
 See Disease Characteristics

Patient Characteristics:

Age:
 18 and over
 
Performance Status:
 ECOG 0-2

Life Expectancy:
 Greater than 3 months

Hematopoietic:
 WBC at least 4,000/mm3 OR normal absolute neutrophil count
 Platelet count at least 100,000/mm3
 Hemoglobin at least 10 g/dL
 
Hepatic:
 Bilirubin no greater than upper limit of normal (ULN)
 SGOT no greater than 1.5 times ULN (no greater than 2 times ULN if alkaline
  phosphatase is normal)
 Alkaline phosphatase no greater than 2.5 times ULN 
 
Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance greater than 50 mL/min

Cardiovascular:
 No significant cardiovascular disease

Pulmonary:
 No significant pulmonary disease

Neurologic:
 No peripheral neuropathy greater than grade 1
 
Other: 
 Not pregnant or nursing
 Effective contraceptive method must be used by fertile patients
 Adequate and nutritionally balanced enteral intake
 No intravenous alimentation as primary calorie source
 No concurrent non-SCCHN malignancies within 3 years, except:
  Curatively treated basal cell carcinoma of the skin
  Curatively treated squamous cell carcinoma of the skin
  Carcinoma in situ of the cervix
 No serious illness or medical condition

Expected Enrollment

A total of 18 to 40 patients will be accrued.

Outline

This is a dose escalation study of docetaxel.

Patients receive intravenous docetaxel over 1 hour on day 1, followed by 
intravenous cisplatin over 4 hours and fluorouracil and leucovorin calcium 
continuous infusions on days 1-4. Subcutaneous filgrastim (G-CSF) and oral 
ciprofloxacin are administered beginning 6-12 hours after chemotherapy. The 
regimen is repeated every 21-35 days, for up to 3 courses. 

Patients experiencing complete or partial response after the first 2 courses 
of chemotherapy receive a third and final course. Patients exhibiting stable 
disease, progression, or unacceptable toxic effects are removed from the study.

During weeks 4 or 5 of cycle 3, patients undergo restaging evaluation. Within 
2 weeks of chemotherapy completion, patients receive radiotherapy 5 days a 
week, for 6-7 weeks.

Upon completion of radiotherapy, patients not achieving a complete response 
undergo a neck dissection.

Cohorts of 3-5 patients each are treated at each dose level of docetaxel. If 2 
or more patients experience dose limiting toxicity at a given dose, the prior 
dose is declared the maximum tolerated dose (MTD). A total of 15 patients is 
treated at the MTD.

Patients are followed every month for the first year.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

A. Dimitrios Colevas, MD, Protocol chair		Ph: 301-496-1106 Email: colevasd@ctep.nci.nih.gov