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High-dose Vorinostat effective at treating relapsed lymphomas
Date:2/4/2013

ective yet against lymphomas, patients who relapse after receiving them are less likely to achieve long-term, disease-free survival when current second-line or "salvage" therapies are applied. This is because the cancers develop resistance to the drugs or the tumor's biology changes in some way to reduce their effectiveness.

Lymphoma refers to a group of cancers that strike the lymphatic system, which is a key part of the immune system. Lymphomas are broadly classified as either Hodgkin or non-Hodgkin. Some lymphomas are highly curable; others require complex treatment.

Preclinical studies at Fred Hutch and other research centers have found Vorinostat to be effective when used along with the standard chemotherapy combo, which is known by the acronym (R)ICE for rituximab, ifosphamide, carboplatin and etoposide. Vorinostat works by blocking signals to tumor-suppressor genes, which allows those genes to induce tumor cell death.

Vorinostat is approved by the Food and Drug Administration to treat cutaneous T-cell lymphoma. The standard dose is 400 milligrams per day. It is manufactured by Merck & Co.

The phase 1 trial involved 27 patients at about a dozen sites that are members of the Puget Sound Oncology Consortium. Because the drugs can be taken orally, the patients could self-treat at home. A novel two-stage dose escalation schedule developed at Fred Hutch was used to speed the time it took to determine the maximum effective dose of Vorinostat with the fewest side effects, which was 500 milligrams twice a day.

Some level of response was observed in 19 patients, including eight complete responses. The most common side effects were gastroenterological, which led researchers to recommend giving future patients preventive medicines while taking Vorinostat.

Because many of the patients were destined for an autologous hematopoietic stem cell transplant as the next treatment step, researchers also evaluated the ability to mobilize and collect the pat
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
Source:Eurekalert

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