RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether methotrexate or paclitaxel is more effective in treating patients with advanced head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of methotrexate with that of paclitaxel in treating patients who have advanced head and neck cancer that cannot be treated with cisplatin.

Condition	Treatment or Intervention	Phase
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity stage IV squamous cell carcinoma of the lip and oral cavity recurrent squamous cell carcinoma of the oropharynx recurrent squamous cell carcinoma of the hypopharynx stage IV squamous cell carcinoma of the nasopharynx stage IV salivary gland cancer recurrent salivary gland cancer stage IV squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity stage IV squamous cell carcinoma of the oropharynx recurrent squamous cell carcinoma of the nasopharynx recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity salivary gland squamous cell carcinoma stage IV squamous cell carcinoma of the hypopharynx	Drug: methotrexate  Drug: paclitaxel	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the progression free survival, median survival, and overall survival in cisplatin-ineligible patients with advanced squamous cell carcinoma of the head and neck following weekly outpatient methotrexate (arm I) versus paclitaxel (arm II).

II. Compare the response rate of patients in the two treatment arms.

III. Compare the Trial Outcome Index scores of patients in the two treatment arms.

IV. Compare the weight change, neurologic toxicity, and mucositis scores of patients in the two treatment arms.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by performance status (0-1 vs 2) and age (less than 60 vs at least 60).

Patients are randomized to receive methotrexate IV bolus every week for 4 weeks (arm I) or paclitaxel IV over 1 hour every week for 4 weeks (arm II).

All patients receive at least 4 weeks of treatment (1 course). Patients continue treatment for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

PROJECTED ACCRUAL: There will be 230 patients accrued into this study over 2.4 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced, incurable, squamous cell carcinoma of thehead and neck
• Recurrent disease in a previously irradiated field must be biopsy proven ordocumented unequivocally by physical exam or radiograph(s)
• Measurable or evaluable disease
• Patients with ECOG performance status of 0-1 must be ineligible for protocolE-1395 and unable to tolerate cisplatin-based therapy for 1 or more of the following reasons: Hearing loss that precludes cisplatin; Unable to handle a fluid load necessitated by cisplatin-based treatment, due to underlying cardiac or pulmonary disease; Mild renal insufficiency (creatinine 1.6-2.0 mg/dL) or creatinine clearance of 40-60 mL/min that would make cisplatin treatment difficult, if not dangerous
• History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy
• No history of carcinomatous meningitis

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy except in the adjuvant, neoadjuvant, or radiosensitizing setting; No prior chemotherapy for recurrent or persistent disease after definitive local therapy; At least 6 months since prior methotrexate or paclitaxel
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; At least 4 weeks since prior radiotherapy
• Surgery: See Disease Characteristics; Recovered from prior surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2 (See Disease Characteristics)
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,800/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; SGOT and SGPT no greater than 5 times upper limit of normal
• Renal: See Disease Characteristics; Creatinine no greater than 2.0 mg/dL; No evidence of symptomatic hypercalcemia
• Cardiovascular: See Disease Characteristics; No active angina or uncontrolled arrhythmias
• Metabolic: No uncontrolled diabetes; No random blood sugar at least 300 mg/dL
• Neurological: No evidence of ongoing grade 2 or greater peripheral sensory neuropathy
• Pulmonary: See Disease Characteristics
• Other: No other concurrent, active, invasive malignancies; No significant detectable infection; Not pregnant or nursing; Effective contraception required of all fertile patients

Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Chicago (Lakeside), Chicago,  Illinois,  60611,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
New Jersey
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
      University of Rochester Cancer Center, Rochester,  New York,  14642,  United States
Ohio
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
Tennessee
      Vanderbilt Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
      Veterans Affairs Medical Center - Nashville, Nashville,  Tennessee,  37212,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Corey Jay Langer,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000066662; E-7397
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003592
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08