Inclusion Criteria:

- Patients must have histologically or cytologically confirmed squamous cell cancer of
the head and neck (MedDRA code 90002024), excluding nasopharyngeal primaries, which
is unresectable or metastatic; the disease must be incurable with surgery or
radiation therapy; the tumor should preferably be present at the primary site, and it
must be accessible to planned biopsy methods

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >
20 mm with conventional techniques or as > 10 mm with spiral CT scan

- Patients may have received any number of prior systemic chemotherapy regimen for
unresectable, recurrent or metastatic disease; chemotherapy must have been completed
at least 4 weeks prior to entry into the study; patients treated previously with
mitomycin C and nitrosoureas should have a therapy-free interval of at least 6 weeks
duration prior to study entry; if patients have received doxorubicin in the past,
their cumulative dose of doxorubicin should not be more than 450 mg/m^2; prior
radiation therapy is allowed but must have been completed at least 4 weeks prior to
study entry; if the only site of measurable disease is a previously irradiated area,
the patient must have documented progressive disease or biopsy-proven residual
carcinoma; persistent disease after radiotherapy must be biopsy-proven at least 8
weeks after the completion of radiotherapy

- Life expectancy of greater than 3 months

- Patients must have normal organ and marrow function as defined by the following labs
performed =< 2 weeks of study entry:

- Leukocytes ≥ 3,000/uL

- Absolute Neutrophil Count ≥ 1,500/uL

- Hemoglobin ≥ 10 gm%

- Platelets ≥ 100,000/uL

- Total Bilirubin =< 1.5 X upper normal institutional limit

- AST(SGOT)/ALT(SGPT) =< 2.5 X upper normal institutional limits

- Creatinine within normal institutional limits OR creatinine clearance ≥ 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- PT/PTT =< 1.1X upper normal institutional limits

- Calcium within normal institutional limits

- CPK, Troponin within normal institutional limits

- Uric Acid within normal institutional limits

- Patients should have a baseline EKG tracing; the screening EKG will be read by the
local cardiologist, who will decide on inclusion or exclusion of the patient based on
cardiac parameters; there should be no history of arrhythmias including atrial
fibrillation, myocardial infarction or congestive heart failure; there should be no
history of cardiac hypertrophy

- Patients must not have a concurrent malignancy except curatively treated basal or
squamous cell carcinoma of the skin or carcinoma in-situ of the cervix; patients with
prior malignancies who have been disease-free > 2 years are eligible

- Patients must not have an active infection nor currently be receiving treatment for a
recent infection

- Patients must have recovered from the effects of any recent surgery

- The effects of depsipeptide on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study
participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately; a
negative serum pregnancy test is required =< 2 weeks of randomization for women who
are still menstruating

- Ability to understand and the willingness to sign a written informed consent
document; in addition to consent for the therapy, patients must give consent to
required pre- and post-therapy blood and tissue samples; because of the relatively
small number of patients studied, biopsies will be required for participation;
rarely, a patient may refuse post-treatment biopsy; in that event, the patient will
be allowed to continue depsipeptide therapy if it is thought by the investigator that
the patient is possibly deriving clinical benefit; the protocol can then possibly
accrue additional patient/s to maintain adequate numbers of samples

Exclusion Criteria:

- Patients who have had palliative chemotherapy or radiotherapy within 4 weeks (6 weeks
for nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients should not have had prior therapy with depsipeptide and may not be receiving
any other investigational agents or drugs known to have histone deacetylase inhibitor
activity such as sodium valproate

- 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 adverse events

- Significant cardiac disease including congestive heart failure that meets New York
Heart Association (NYHA) class III and IV definitions (see Appendix II), history of
myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or
poorly controlled angina

- History of serious ventricular arrhythmia (VT or VF, > 3 beats in a row), QTc > 500
msec, or LVEF < 40%

- Patients may not be co-medicated with an agent that causes QTc prolongation; also,
patients may not be co-medicated with hydrochlorothiazide (HCTZ), an agent possibly
associated with adverse events related to depsipeptide; patients who are taking HCTZ
should have this medication stopped or switched to an acceptable potassium-conserving
agent or other anti-hypertensive medication; patients taking warfarin concurrently
with depsipeptide therapy will be monitored for elevations in INR, as a potential
drug interaction exists

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because depsipeptide has unknown but
potential risk for teratogenic or abortifacient effects; however, there is no
evidence that depsipeptide itself is teratogenic or abortifacient; because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with depsipeptide, breastfeeding should be discontinued if
the mother is treated with depsipeptide

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, known HIV-positive patients
receiving combination anti-retroviral therapy are excluded from the study because of
possible pharmacokinetic interactions with depsipeptide