Phase I Trial of Valproic Acid and Epirubicin in Solid Tumor Malignancies

Inclusion Criteria:

- Patients must have cytologically/histologically documented solid tumor malignancies

- Age > 18 years old

- Patients must have ECOG performance status 0-2

- Patients must be able to give informed consent and able to follow guidelines given in
the study

- The patient has no major impairment of hematological function, as defined by the
following laboratory parameters: WBC >3.0x109/L; ANC > 1.5 x 109/L; Hgb >9.0g/dL; PLT
>100x109/L (untransfused). Red blood cell transfusions and repeat evaluations for
study entry are allowed

- All patients of reproductive potential must use an effective method of contraception
during the study and six months following termination of treatment. (Not applicable
to patients with bilateral oophorectomy and/or hysterectomy or to female patients who
are older than 50 years and have not had a menstrual cycle in more than one year.

- Patients must have measurable or evaluable disease by staging studies performed
within 4 weeks of enrollment (evaluable disease refers to ovarian cancer with an
elevated CA-125 or prostate cancer with elevated PSA only)

- Once MTD for VPA and epirubicin is reached, the trial will be limited to patients
with breast cancer

- At the MTD for VPA and FEC MTD for the trial will be expanded to 15 patients with
advanced (inflammatory, Stage >IIIB or regional stage IV) or metastatic breast
cancer.

- Patients must have biopsiable disease and be willing to undergo pre and post-VPA
biopsies in cycle 1; Patients must have measurable disease, Patients from the last
cohort may be included if they were biopsied

Exclusion Criteria:

- Patients may not have had cumulative anthracycline exposure greater than doxorubicin
300 mg/m2 or epirubicin 600 mg/m2.

- Patients must not have evidence of significant active infection (e.g., pneumonia,
cellulitis, wound abscess, etc.) at time of study entry.

- Patients must have adequate renal and normal hepatic function (creatinine < 1.5 x
upper limit of normal (ULN), bilirubin and SGOT (AST), SGPT (ALT) within 1.5 x the
upper institutional normal limits) obtained within 4 weeks prior to registration.

- Pregnant and breast feeding women are excluded from the study because effects on the
fetus are unknown and there may be a risk of increased fetal wastage.

- Women of childbearing age must have a negative pregnancy test and be willing
to use a highly effective method of contraception. Men who are sexually active must
also be willing to use an accepted and effective method of contraception.

- Patients taking anti-arrhythmic medication or with a history of cardiac failure or
with ejection fraction £ 50 % are excluded. Patients with a history of long QT
syndrome are excluded from study. Patients with a history of ventricular tachycardia
or fibrillation are also excluded. Patients must have normal sinus rhythm and normal
PR and QT intervals on EKG.

- Patients with uncontrolled CNS metastasis or a history of seizures are excluded.
Patients with stable CNS metastasis (either surgically resected, treated with gamma
knife or stable for 3 months following WBRT are eligible)

- Patients with stable brain metastases will need an MRI within 4 weeks prior to start
of therapy