In a Phase II open label study with investigational oral SuberoylAnilide Hydroxamic Acid ( SAHA ), a new class of anti-tumor agents that inhibits histone deacetylase, eight of 33 patients with advanced, refractory cutaneous T-cell lymphoma ( CTCL ) experienced partial responses ( physician assessment of >50 percent reduction in overall disease burden ), the primary endpoint of the study.

" In this study, SAHA demonstrated encouraging improvements in the overall condition of patients with advanced, refractory, and heavily pretreated CTCL as assessed by their physician's global assessments," said Madeleine Duvic, M.D., at M.D. Anderson Cancer Center and lead investigator of the study. " SAHA was shown to reduce the tumor burden and improve pruritus in CTCL patients, especially those with erythroderma and Sezary Syndrome. A second Phase IIb study is underway to confirm these results. "

The 33 patients in the study ( median age 67 ) were treated in one of three dosing cohorts.
In the first cohort, 13 patients received 400 mg once daily until disease progression or an adverse event. In the second cohort, 11 patients received 300 mg twice a day for three to five days a week for 16 weeks. In the third cohort, nine patients received 300 mg twice a day for 14 days, no therapy for the following seven days, and then 200 mg twice a day continuously.

The most common side effects seen in the study were fatigue ( 85 percent ), diarrhea ( 58 percent ), nausea ( 61 percent ), change in taste ( 58 percent ), dry mouth ( 42 percent ), decreased appetite ( 21 percent ), and low platelet count ( 30 percent ).

SAHA is believed to inhibit the enzyme histone deacetylase ( HDAC ).
Histones are structural proteins around which DNA coils.
These proteins may play an important role in the regulation of gene expression. Increased levels of HDAC, which are present in tumor cells, trigger histones to tightly package DNA and limit the transcription of tumor suppressor genes. By changing the balance between acetylated and deacetylated proteins, SAHA causes cell cycle arrest, cell differentiation, and apoptosis.

Cutaneous T-cell lymphoma, a type of non-Hodgkin's lymphoma, is a slow-growing form of cancer in which some of the body's white blood cells known as T-lymphocytes become malignant.
In CTCL, the malignant T-cells are drawn to the skin, where some are deposited. Patients usually develop CTCL after age 50.
Cutaneous T-cell lymphoma affects 20,000 patients in the United States, with another 1,500 new cases reported each year.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005