Valproic Acid in Treating Patients With Kaposi's Sarcoma

A Pilot Trial Of Valproic Acid In Patients With Kaposi's Sarcoma

RATIONALE: Valproic acid may help stop the growth of Kaposi's sarcoma cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: This clinical trial is studying valproic acid in treating patients with HIV-related Kaposi's sarcoma.

OBJECTIVES:

Primary

• Determine the safety of valproic acid in patients with Kaposi's sarcoma.
• Determine the effects of this drug on human herpes virus 8 (KSHV) gene expression using polymerase chain reaction and immunohistochemistry in these patients.

Secondary

• Determine the effects of this drug on HIV, KSHV, and Epstein-Barr virus viral loads in the plasma and peripheral blood mononuclear cells of these patients.
• Determine clinical response in patients treated with this drug.

OUTLINE: This is an open-label, pilot, multicenter study.

Patients receive oral valproic acid twice daily on days 1-28 followed by a drug taper over 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed HIV-related Kaposi's sarcoma (KS)

  • Disease involving the skin and/or lymph nodes

    • No symptomatic visceral disease
    • No oral KS as the only site of disease

  • Slowly progressive or stable disease allowed

    • Slow progression defined as fewer than 5 new lesions per month

  • Must have documented HIV infection by positive ELISA, western Blot, or viral load determination

• CD4 T-cell count > 50/mm^3

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥ 750/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)*
• AST and ALT ≤ 3 times ULN
• Albumin > 2.5 g/dL NOTE: *Elevated total bilirubin (≤ 3.5 mg/dL) secondary to indinavir therapy allowed provided the direct bilirubin is normal

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No prior myocardial infarction
• No evidence of cardiac ischemia

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No prior lactic acidosis > 2.0 mmoles/L
• No prior lipoatrophy or hypercholesterolemia secondary to retroviral treatment
• No concurrent, acute, active opportunistic infection other than oral thrush or genital herpes within the past 14 days
• No other concurrent neoplasm requiring cytotoxic therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior biologic therapy for KS

Chemotherapy

• More than 2 weeks since prior chemotherapy for KS
• No concurrent systemic cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 2 weeks since prior radiotherapy for KS

Surgery

• Not specified

Other

• More than 2 weeks since other prior antineoplastic or local therapy for KS
• More than 2 weeks since prior investigational therapy for KS
• More than 60 days since prior local therapy to a KS-marker lesion unless lesion has clearly progressed since therapy
• More than 1 year since prior valproic acid
• Concurrent antiretroviral therapy allowed provided regimen has been stable for at least 4 weeks
• No concurrent zidovudine
• No other concurrent KS-specific therapy
• No other concurrent investigational drugs, other than IND-approved antiretroviral agents