RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining bortezomib with radiation therapy may kill more tumor cells

PURPOSE: Phase I trial to study the effectiveness of combining bortezomib with radiation therapy in treating patients who have recurrent or metastatic head and neck cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of bortezomib with concurrent radiotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

OUTLINE: This is a dose-escalation study. Patients are stratified according to prior radiotherapy (yes vs no).

Patients receive bortezomib IV over 3-5 seconds twice weekly. Patients also receive radiotherapy on days 1-5 (days 2-5 only for the first course). Courses repeat every week for 3 weeks. Patients then receive radiotherapy alone on days 1-5 of weeks 4 and 5. Treatment with bortezomib and radiotherapy resumes in weeks 6 and 7 (for patients with prior radiotherapy) or weeks 6, 7, and 8 (for patients with no prior radiotherapy) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at weeks 1-8, at week 12, and then monthly for 1 year.

PROJECTED ACCRUAL: A maximum of 51 patients (30 with prior radiotherapy and 21 with no prior radiotherapy) will be accrued for this study within 12 months.

• Drug: bortezomib
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck

  • Local-regional disease that is amenable to radiotherapy
  • Persistent, recurrent, or unresectable regional disease with OR without metastatic disease after standard curative therapy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2 OR
• Karnofsky 50-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT less than 2.5 times ULN

Renal:

• Creatinine less than 1.5 times ULN OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No myocardial infarction within the past 6 months
• No unstable angina pectoris
• No unstable cardiac arrhythmia requiring assessment for clinical intervention

• No postural hypotension due to severe baroreceptor dysfunction after prior radiotherapy and/or surgery that is not amenable to volume repletion, defined as 1 of the following:

  • Systolic blood pressure remains at 100 mm Hg or less with absence of orthostatic changes or symptoms
  • Systolic blood pressure remains at 120 mm Hg or less with orthostatic changes and absence of symptoms
• No uncorrectable hyponatremia of 130 mEq/L or greater

Other:

• No known HIV positivity
• No other prior malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No concurrent uncontrolled illness
• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• No concurrent biologic therapy for treatment of malignancy
• No concurrent colony-stimulating factors during first course of study therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy and recovered
• No other concurrent chemotherapy for treatment of malignancy

Endocrine therapy:

• No concurrent endocrine therapy for treatment of malignancy

Radiotherapy:

• More than 6 months since prior radiotherapy to the head and neck

  • At least 1 month since prior palliative radiotherapy to any other sites and recovered

Surgery:

• At least 4 weeks since prior surgery

Other:

• No other concurrent investigational agent or therapy for treatment of malignancy
• No concurrent amifostine