Methotrexate Compared With Paclitaxel in Treating Patients With Advanced Head and Neck Cancer

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.

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.

DISEASE CHARACTERISTICS: Histologically confirmed advanced, incurable, squamous cell
carcinoma of the head and neck Recurrent disease in a previously irradiated field must be
biopsy proven or documented unequivocally by physical exam or radiograph(s) Measurable or
evaluable disease Patients with ECOG performance status of 0-1 must be ineligible for
protocol E-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

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

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