| Exclusion Criteria: | 1) Patients who have had chemotherapy or radiotherapy within 2 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 2 weeks earlier.
2) Patients who have taken valproic acid, a histone deacetylase inhibitor, within 2 weeks prior to entering the study.
3) Patients may not be receiving any other investigational agents.
4) Patients with known brain metastases are 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.
5) History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA.
6) Patients who had significant side effects and poor tolerance to gemcitabine chemotherapy in the past or history of allergy to gemcitabine in the past.
7) 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.
8) Pregnant women are excluded from this study because SAHA 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 SAHA, breastfeeding should be discontinued if the mother is treated with SAHA. These potential risks also apply to gemcitabine.
9) HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SAHA. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. |