New NCCN Guidelines to Incorporate Approved New Treatment Options

Two recent FDA approvals have prompted the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world's leading cancer centers dedicated to improving the quality and effectiveness of care provided to patients with cancer, to update the NCCN Clinical Practice Guidelines in Oncology™ for Non-Hodgkin's Lymphomas to include ofatumumab (Azerra™, GlaxoSmithKline) and romidepsin (Istodax®, Gloucester Pharmaceuticals) as treatment options for select patients with two types of Non-Hodgkin's Lymphomas.

Ofatumumab was added to the NCCN Guidelines as a treatment option for relapsed/refractory disease in patients with chronic lymphocytic leukemia (CLL), with and without a 17p deletion. A 17p deletion refers to a chromosomal abnormality involving deletion of genetic material from chromosome 17. Ofatumumab was approved by the FDA on October 27, 2009 for patients with CLL, a slowly progressing cancer of the blood and bone marrow, whose cancer is no longer responding to other chemoimmunotherapy regimens.

In addition, the updated NCCN Guidelines now include romidepsin as a suggested systemic treatment option for patients with mycosis fungoides and Sezary syndrome, two of the most common types of cutaneous T-cell lymphoma (CTCL). On November 6, 2009, the FDA approved romidepsin, a histone deacetylase (HDAC) inhibitor, for the treatment of CTCL in patients who have received at least one prior systemic therapy.

These latest additions come shortly after another recent update to the NCCN Guidelines for Non-Hodgkin's Lymphomas that incorporated the FDA approval of pralatrexate (Folotyn™, Allos Therapeutics, Inc.) for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL).

The NCCN Clinical Practice Guidelines in Oncology(TM) are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of physicians from NCCN Member Institutions.

Romidepsin (Istodax) approved for the treatment of Cutaneous T-cell Lymphoma (CTCL)

The U.S. Food and Drug Administration has approved romidepsin (Istodax), an injectable medication, for treatment of patients with a rare form of cancer known as Cutaneous T-cell Lymphoma (CTCL).

Cutaneous T-cell lymphoma is a slow-growing cancer of infection-fighting white blood cells called T-lymphocytes. Most cases start with dry skin, red rash, and itching that can become severe. The skin may develop tumors that can become ulcerated, causing infection. In some cases, CTCL spreads to the blood, lymph nodes, or internal organs. There are about 1,500 new cases of CTCL every year in the United States.

Patients with localized CTCL on the skin are treated with topical agents or phototherapy, but chemotherapy may be used if the cancer advances.

Romidepsin interferes with processes required for cell replication. It is intended to be used in patients when CTCL gets worse or comes back after at least one other type of chemotherapy has been used.

“This approval demonstrates FDA’s commitment to the development and approval of drugs for rare and uncommon diseases,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. The FDA approved Istodax on Nov. 6, 2009.

Previous drug treatment approvals for CTCL included vorinostat (Zolinza, Merck & Co., Inc), denileukin difitox (Ontak, Eisai Inc), and bexarotene (Targretin, Eisai Inc).

Romidepsin was evaluated based on two clinical studies involving a total of 167 patients. About 35 percent of patients in both of the trials experienced tumor responses, indicating a reduction of the size of tumors. Responses lasted a median of 15 months in one study and 11 months in the other study. Six percent of those studied had complete responses, indicating no apparent evidence of the tumor on physical, laboratory, and X-ray examinations.

Common side effects include nausea, fatigue, infections, vomiting, decreased appetite, decreased red blood cell count, decreased platelet count, and decreases in the components of white blood cells.
Romidepsin may cause changes in an electrocardiogram (ECG). Periodic blood tests should be done to monitor electrolytes, and periodic ECG monitoring should be considered in patients at risk for certain heart rhythm abnormalities. Romidepsin may harm a fetus and women should not become pregnant while taking the drug.

Romidepsin is marketed by Gloucester Pharmaceuticals Inc. of Cambridge, Mass.