PS-341 and Radiation to Treat Advanced Cancer of the Head and Neck

• INCLUSION CRITERIA

Patients must meet the following inclusion criteria:

Patients with histologically confirmed SCCHN which is persistent or recurrent and unresectable; or patients presenting with or developing distant metastases following standard curative measures, and who have local regional disease amenable to radiation or re-irradiation therapy are eligible. Patients with a history of treatment for other prior malignancy will be eligible, provided they remain disease-free more than 2 years after initial treatment, or were treated for non-melanoma skin cancer, or in situ cervical cancer.

Because of greater potential for acute toxicity in previously irradiated patients, patients will be stratified based on whether they have received prior radiation. Stratum A: Prior radiation therapy (greater than 6 months) with or without prior surgery or chemotherapy. Stratum B: No prior radiation therapy, but greater than or equal to 4 weeks after surgery or chemotherapy.

Age greater than 18 years of age. Because no dosing or toxicity data are currently available on the use of PS-341 in patients less than 18 years of age, children are not included in this study. Further, SCCHN in patients less than 18 years of age is exceedingly rare.

ECOG performance status less than or equal to 2 (Karnofsky greater than 50%).

Life expectancy greater than 3 months.

Patients must have adequate organ and marrow function as defined below:

absolute neutrophil count is greater than 1,500/microliter

platelets are greater than 100,000/microliter

total bilirubin is less than 1.5 times the ULN

AST(SGOT)/ALT(SGPT) is less than 2.5 times the ULN

serum creatinine is less than 1.5 times the ULN

or<TAB>

creatinine clearance greater than 60 mL/min/1.73 m(2) for patients with creatinine levels equal to or greater than 1.5 times the ULN.

The effects of PS-341 on gametogenesis and the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men and women of child-bearing potential must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or a participating spouse are enrolled in this study, she should inform her treating physician immediately.

Because the potential risk of toxicity in nursing infants secondary to PS-341 treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with PS-341.

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Patients who have had surgery, chemotherapy, or immunotherapy within 4 weeks, or radiotherapy to the head and neck within 6 months prior to entering the study. For palliative radiation at the sites, at least one month must elapse between the end of radiation and the beginning of therapy under this protocol and toxicities must have resolved.

Patients undergoing therapy with other investigational agents.

Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities.

Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina pectoris, or unstable cardiac arrhythmia, requiring assessment for clinical intervention.

Pregnant and nursing women are excluded from this study because PS-341 is an investigational agent with unknown effects on the fetus and nursing infant.

HIV-positive patients are excluded from the study because of possible pharmacokinetic interactions with medication necessary to control HIV or its complication and owing to uncertain interaction of PS-341 with immune function.

Patients with postural hypotentsion due to severe baroreceptor dysfunction after previous radiation and/or surgery defined as a) postural hypotension that cannot be corrected with volume repetition to systolic blood pressure greater than 100 mm Hg and absence of orthostatic changes or symptoms; b) postural hypotension that cannot be corrected with volume repletion to systolic blood pressure greater than 120 mm Hg with orthostatic changes and absence of symptoms.

Patients with hyponatremia not correctable to greater than or equal to 130 mEq/L will be excluded.