Novel Therapy - romidepsin (depsipeptide/FK228)

Romidespin (formerly called depsipeptide or FK228) is a novel anti-cancer agent being studied for the treatment of T-cell Non-Hodgkin's Lymphoma. Specifically it is in stage II trials for cutaneous T-cell lymphomas (CTCL) such as Mycosis Fungoides and Sezary Syndrome and studies are planned for peripheral t-cell lymphoma (PTCL) and possibly other types of cancer. It usually comes in liquid form which is given by vein. The drug acts as a histone deacetylase inhibitor (HDACi), loosening DNA which may allow some genes to be turned on and others turned off. This interaction ultimately leads to apoptosis (death of the cancer cells).

History: The drug was discovered by Fujisawa Pharmaceutical Co., Ltd. and initially tested in clinical trials at the US National Cancer Institute. Today, Gloucester Pharmaceuticals has worldwide development and commercialization rights and is conducting clinical trials in various cancers.

Before taking this medicine: Inform your doctor or pharmacist of all prescription and over-the-counter medicines you take. Inform your medical doctor of any other medical conditions or allergies or if you are pregnant or breast feeding.

Dosing: This drug is administered in your doctor's office, once per week for 3 weeks followed by 1 week of rest. This is known as 1 cycle of treatment. The number of cycles each patient receives is determined by how well they respond and tolerate the drug.

Short Term Side Effects: Romidepsin can cause nausea and vomiting, low white blood cell count and fatigue in some patients. Your doctor may prescribe additional medications to help with this. Some anti-nausea drugs are known to have an effect on the heart QT interval (as seen and measured in a electrocardiogram/EKG test) and should be avoided. Kytril is the recommended anti- nausea drug in current clinical trials with romidepsin, as it has the least effect on QT intervals in its class of drugs. Other drugs may also lengthen QT - tell your physician of all prescription and non-prescription medications you may take.

Long Term Side Effects: As this drug is still in clinical trials and has only been studied since 1996, long term effects have yet to be determined but Gloucester has yet to see any long-term effects to date.

Clinical Trial Information: romidepsin is currently being studied both hematologic and solid tumor malignancies. Trials are being conducted by Gloucester Pharmaceuticals or the National Cancer Institute (NCI), under a Cooperative Research and Development Agreement (CRADA) with Gloucester. For more information about ongoing Cutaneous T-cell Lymphoma (CTCL) clinical studies please visit : http://www.clinicaltrials.gov/ct/show/NCT00106431

CTCL Trial Brochure (PDF format)

(this is currently medically oriented)

Resources

• Manufacturer Website Information (www.gloucesterpharma.com)

• Lerner et al. "Romidepsin (Depsipeptide, FK228) Induces Clinically Significant Responses in Treatment-Refractory CTCL: Interim Report of a Phase II Multicenter Study", Abstract #2468, ASH 48th Annual Meeting, December 10, 2006, www.hematology.org

• Piekarz et al. "Phase II Trial of Romidepsin, FK228, in Cutaneous and Peripheral T-Cell Lymphoma: Clinical Activity and Medical Markers", Abstract #2469, ASH 48th Annual Meeting, December 10, 2006, www.hematology.org

• Piekarz R, et al. Completion of the First Cohort of Patients with Cutaneous T-Cell Lymphoma Enrolled on a Phase II Trial of Depsipeptide. Blood (ASH Annual Meeting Abstracts), Nov 2005; 106: Abstract 231.

• Journal Article: T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. Piekarz RL, Robey RW, Zhan Z, Kayastha G, Sayah A, Abdeldaim AH, Torrico S, Bates SE. Blood. 2004 Jun 15;103(12):4636-43. Epub 2004 Mar 2 PubMed

• Additional articles are available in PubMed - suggested search terms are depsipeptide, romidepsin and lymphoma

Manufacturer

In April 2004, Gloucester Pharmaceuticals acquired the worldwide development and commercialization rights to its lead clinical candidate, romidepsin (also known as depsipeptide or FK228), through a licensing agreement with Fujisawa Pharmaceutical Co., Ltd.

Gloucester Pharmaceuticals

One Broadway, 14th Floor

Cambridge, MA 02142 USA

Tel: 888-474-2825 or 617-583-1366; Fax: 617-583-1368

Email: [email protected]

Related Articles

For more information on Non-Hodgkin's Lymphoma, please see the following pages:

Adult Nonhodgkin's Lymphoma: Chemotherapy

Adult Non-Hodgkin's Lymphoma: Treatment

Adult Non-Hodgkin's Lymphoma: Introduction