OBJECTIVES:

• Compare the response rate in patients with metastatic or recurrent squamous cell carcinoma of the head and neck treated with 2 different dosing schedules of ixabepilone.
• Compare the toxicity of these drug schedules in these patients.
• Correlate survivin expression with therapeutic responsiveness to this drug in these patients.
• Correlate changes in tumor vascular density and endothelial cell apoptosis with outcome in patients treated with this drug.

OUTLINE: This is a randomized study. Patients are stratified according to prior taxane therapy (yes vs no) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

In both arms, patients achieving complete response (CR) receive 2 additional courses past CR if a minimum of 6 courses have been administered.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 64-144 patients (16-36 per stratum) will be accrued for this study within 8-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck (SCCHN) that is incurable with surgery or radiotherapy

  • No nasopharyngeal primaries

• Measurable disease

  • If the only site of measurable disease is in a previously irradiated area, then patient must have documented disease progression or biopsy-proven residual carcinoma
  • Persistent disease after radiotherapy must be biopsy proven at least 8 weeks after completion of radiotherapy
• Must have distant metastases or locoregional recurrence or persistent disease within a prior radiation portal

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.2 mg/dL OR
• Creatinine clearance at least 50 mL/min
• Calcium normal
• No prior malignancy-associated hypercalcemia

Other:

• No other prior or concurrent malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No grade 2 or greater pre-existing peripheral neuropathy
• No active infection
• No greater than grade 1 or uncomplicated, non-recurrent grade 2 hypersensitivity reaction to castor oil, agents containing Cremophor EL, or paclitaxel
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy
• No more than 1 prior biologic therapy regimen

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for recurrent and/or metastatic SCCHN
• No prior investigational taxane
• Prior docetaxel or paclitaxel allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery:

• Recovered from prior surgery

Other:

• No concurrent treatment for a recent infection