INCLUSION CRITERIA:
1. Patients must have histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients who have not received any prior therapy for malignancy are also eligible if they are ineligible for standard therapy due to hepatic dysfunction. Patients with a liver mass, raised Alpha-fetoprotein level (greater than or equal to 500ng/mL) and positive serology for hepatitis, consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis.
2. Age greater than or equal to 18 years.
3. Life expectancy of greater than 3 months.
4. ECOG performance status less than or equal to 2.
5. Patients must have acceptable renal and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1.5 times 10(9)/L.
- platelets greater than or equal to 100 times 10(9)/L.
- creatinine within normal institutional limits.
OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
6. Patients with abnormal liver function will be eligible and will be grouped according to the criteria in Section 5.1. Patients with active hemolysis should be excluded. No distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes. Liver function tests should be repeated within 48 hours prior to starting initial therapy.
7. Patients with gliomas or brain metastases who require corticosteroids or anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment. Patients with known brain metastases should have had brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the protocol.
8. Patients with biliary obstruction for which a shunt has been placed are eligible, provided the shunt has been in place for at least 10 days prior to the first dose of vorinostat and the liver function has stabilized. Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function. There should be no evidence of biliary sepsis.
9. The effects of vorinostat on the developing human fetus are unknown. For this reason and because HDAC inhibitors may be teratogenic, women of childbearing 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.
10. Ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
1. Patients who have had chemotherapy or radiotherapy within 3 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 3 weeks earlier. Patients who have been treated with agents that persist in the body for longer than 4 to 6 weeks (such as suramin) are ineligible during the elimination period for those agents.
2. Patients must not have had a major surgery within 14 days prior to registration/treatment.
3. Patient may not have received prior therapy with vorinostat. Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment.
4. Patients may not have received any other investigationsl agents within 4 weeks of study enrollment.
5. Patients with unstable or untreated (non-irradiated) 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.
6. Inability to take oral medications on a continuous basis.
7. Patients on therapy with enzyme-inducing anticonvulsants.
8. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Pregnant women are excluded from this study because vorinostat is a HDAC inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat.
10. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with vorinostat. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. However, HIV-positive patients without an AIDS-defining diagnosis who are not receiving agents with the potential for PK interactions with vorinostat may be eligible.